HUGO ID Detailed Result 6018

HUGO ID 6018
Symbol IL6
Name interleukin 6 (interferon, beta 2)
#Occurrence 287
#Paper 25

 

PMID Match String Actual String Score Flanking text Edited by Edit
9562310IL-6IL-61.3We assayed IL-6 in 105 cerebrospinal fluid (CSF) CSF samples from patients with 
9562310IL-6IL-61.3There was considerable overlap in IL-6 levels in all patient groups 
9562310IL-6IL-61.3The mean IL-6 in 27 patients with ALS was significantly higher than in 
9562310IL-6IL-61.3Overall CSF IL-6 correlated with protein concentration but not with percentage IgG or 
9562310IL-6IL-61.3CSF oligoclonal bands were no more likely to have detectable IL-6 than patients without oligoclonal bands 
9562310IL-6IL-61.3Similarly IL-6 did not correlate with clinical disease activity in MS when 
9562310IL-6IL-61.3The elevated IL-6 in ALS may reflect an ongoing humoral immune response or 
9562310IL-6IL-61.3in ALS may reflect an ongoing humoral immune response or IL-6 may be non-specifically expressed in these patients as a putative 
9562310IL-6IL-61.3IL-6 is a B cell differentiation factor that was first described 
9562310IL-6IL-61.3Cerebrospinal fluid (CSF) CSF levels of IL-6 are consistently elevated in herpes simplex virus encephalitis and other 
9562310IL-6IL-61.3IL-6 was detected in experimental allergic encephalomyelitis CSF ( Gijbels et 
9562310IL-6IL-61.3central nervous system involvement ( Hirohata and Miyamoto 1990 but IL-6 was not detected in multiple sclerosis (MS) MS ( Houssiau 
9562310IL-6IL-61.3Reports of IL-6 in non-inflammatory CNS disease prompted the present study of CSF 
9562310IL-6IL-61.3found a higher frequency of detection and higher levels of IL-6 in ALS than in the other neurological disease control group 
9562310IL-6IL-61.3In contrast there was no significant difference in CSF IL-6 in either MS or HAM patients compared to other neurological 
9562310IL-6IL-61.3and there was no correlation of CSF immune parameters and IL-6 levels 
9562310IL-6IL-61.3These results are consistent with the hypothesis that CSF IL-6 in ALS has an non-immune origin occurring as a neurotrophic 
9562310IL-6IL-61.3The IL-6 dependent hybridoma cell line MH6OBSF2 ( Matsuda et al. 1988 
9562310IL-6IL-61.3Without IL-6 in the media no viable cells remained in this subclone 
9562310IL-6IL-61.3IL-6 was quantitated by reference to a dose calibration curve of 
9562310IL-6IL-61.3by reference to a dose calibration curve of recombinant human IL-6 (kindly kindly supplied by Drs Hirano and Kishimoto assayed with 
9562310IL-6IL-61.3CSF IL-6 values were expressed as log 1 0 pg/ml pg ml 
9562310IL-6IL-61.3The sensitivity of IL-6 detection was determined to be 1.6 pg/ml pg ml 
9562310IL-6IL-61.3human cytokines (IL-1 IL-1 IL-1_amp_#x3b2 IL-2 TNF and abrogating the IL-6 effect by anti-IL-6 polyclonal antibody (Genzyme, Genzyme Boston MA 
9562310IL-6IL-61.3boundary of detectability of 1.6 pg/ml pg ml for the IL-6 assay (or or log 1 0 IL-6 of 0.2 non-parametric 
9562310IL-6IL-61.3ml for the IL-6 assay (or or log 1 0 IL-6 of 0.2 non-parametric techniques were used 
9562310IL-6IL-61.3As shown in Fig 1 there was considerable overlap in IL-6 levels in all patient groups 
9562310IL-6IL-61.3Table 2 shows IL-6 detection in 78% of 27 patients with ALS (median median 
9562310IL-6IL-61.3of 27 patients with ALS (median median log 1 0 IL-6 of 1.01 55% of 20 patients with MS (median median 
9562310IL-6IL-61.3non-parametric Wilcoxon rank-sum test showed a significant difference in CSF IL-6 between the ALS and OND group ( P =0.0075 but 
9562310IL-6IL-61.3MS and HAM groups all had statistically significant higher mean IL-6 levels than the non-neurological disease control P _amp_#x3c 0.0001 for 
9562310IL-6IL-61.3The greatest CSF IL-6 level in the ALS group (log log 1 0 IL-6 
9562310IL-6IL-61.3IL-6 level in the ALS group (log log 1 0 IL-6 of 2.55 was a sample from the National Neurological Research 
9562310IL-6IL-61.3Although these results failed to show a higher mean IL-6 level in patients with recognized immune-mediated CNS disease (MS MS 
9562310IL-6IL-61.3To determine if IL-6 varies with the activity of immune-mediated disease data from the 
9562310IL-6IL-61.3results in Fig 2 show no significant difference in CSF IL-6 levels with 7 of 12 patients in relapse having detectable 
9562310IL-6IL-61.3levels with 7 of 12 patients in relapse having detectable IL-6 compared to 4 of 8 patients with MS in remission 
9562310IL-6IL-61.3consistent with fluctuating immune-mediated activity in the CNS the CSF IL-6 levels remained at undetectable levels in all four spinal taps 
9562310IL-6IL-61.3To evaluate further any correlation of CSF IL-6 with the extent of immune-mediated activity in the CNS CSF 
9562310IL-6IL-61.3CSF parameters were compared in patients with and without detectable IL-6 
9562310IL-6IL-61.3a significantly higher total IgG in MS patients with detectable IL-6 levels (not not shown but this correlation was not seen 
9562310IL-6IL-61.3percent IgG was higher in the ALS group with detectable IL-6 but not in the combined patient group (not not shown 
9562310IL-6IL-61.3total CSF protein was significantly higher in patients with detectable IL-6 
9562310IL-6IL-61.3in Table 3 mean CSF protein in patients with detectable IL-6 was 49.0_amp_#xb1 3.8 compared to 33.2_amp_#xb1 3.0 in patients with 
9562310IL-6IL-61.349.0_amp_#xb1 3.8 compared to 33.2_amp_#xb1 3.0 in patients with undetectable IL-6 ( P _amp_#x3c 0.01 
9562310IL-6IL-61.3Fig 4 shows CSF IL-6 levels in 35 patients with MS or HAM who had 
9562310IL-6IL-61.3Although the IL-6 level was slightly higher in patients without oligoclonal bands and 
9562310IL-6IL-61.3in patients without oligoclonal bands and the percentage of detectable IL-6 was higher (67% 67% versus 43% these differences were not 
9562310IL-6IL-61.3We found a modest but statistically significant elevation of CSF IL-6 in ALS patients ( Fig 1 
9562310IL-6IL-61.3studies a similar percentage of ALS patients had undetectable CSF IL-6 (6/27 6 27 versus 2/15); 2 15 but 37% of 
9562310IL-6IL-61.3versus 2/15); 2 15 but 37% of our patients had IL-6 levels greater than 10 pg/ml pg ml compared to only 
9562310IL-6IL-61.3The IL-6 levels in ALS CSF (less less than 0.96 log 10 
9562310IL-6IL-61.3Nevertheless the modest IL-6 elevation noted here may be related to an ongoing humoral 
9562310IL-6IL-61.3Serum IL-6 was not measured in ALS but prior studies have shown 
9562310IL-6IL-61.3not measured in ALS but prior studies have shown that IL-6 can concentrate in the CSF compartment (e.g e.g during active 
9562310IL-6IL-61.3IL-6 along with TNF- has been reported to be highly expressed 
9562310IL-6IL-61.3expression we did not find a statistically significant elevation of IL-6 in MS CSF 
9562310IL-6IL-61.3Moreover we were unable to document an increase in IL-6 during active disease both within a group of MS patients 
9562310IL-6IL-61.3et al. 1990 and Maimone et al. 1991 to correlate IL-6 and CSF parameters of immune mediated disease including percentage IgG 
9562310IL-6IL-61.3in the MS and HAM patients suggests either (I) I IL-6 does not play a major role in these disease or 
9562310IL-6IL-61.3major role in these disease or (II) II detection of IL-6 is unreliable in the CSF of immune-mediated CNS parenchymal disease 
9562310IL-6IL-61.3immune-mediated CNS parenchymal disease (because because of instability or because IL-6 from brain in these disease does not enter the CSF 
9562310IL-6IL-61.3It is possible that the IL-6 elevation in ALS is of non-immune origin 
9562310IL-6IL-61.3IL-6 has been shown to induce neuronal differentiation ( Satoh et 
9562310IL-6IL-61.3Moreover IL-6 has been shown to increase in brain in response to 
9562310IL-6IL-61.3We speculate that IL-6 may be produced by astrocytes or microglial cells in ALS 
9562310IL-6IL-61.3This non-specific effect may explain the slightly higher levels of IL-6 in OND controls compared to non-neurological disease controls 
9562310IL-6IL-61.3helpful to distinguish an immune versus a non-immune origin of IL-6 
9562310IL-6IL-61.3CSF IL-6 levels in ALS MS (including including relapsing remitting and stable 
9562310IL-6IL-61.3CSF IL-6 levels in MS patients with either relapsing or remitting/stable remitting 
9562310IL-6IL-61.3CSF IL-6 levels in MS or HAM patients that either have (OCB+) 
10525172IL-6IL-61.0Microglial cells can be activated by pro-inflammatory cytokines IL-1 IL-6 and TNF_amp_#x3b1 as well as by _amp_#x3b2 -amyloid peptide (_amp_#x3b2;-A) 
14511332IL-6IL-61.0Levels of IL-1beta IL-6 and tumour necrosis factor-alpha were found to be elevated in 
14511332IL-6IL-61.0to high expression of COX-2 in sALS particularly IL-1beta and IL-6 
14511332IL-6IL-61.0IL-1beta and IL-6 are assumed to derive from glia 
14511332IL-6IL-61.0COX-2 in CRC parallels the expression of IL-1 beta and IL-6 in CRC ( Maihofner et al . 2003 
15081582IL-6IL-61.3that can induce COX-2 via the cytokines TNF IL-1_amp_#x3b2 and IL-6 
15453089IL-6IL-61.0the prominent microglial activation classical pro-inflammatory mediators such as IL-1 IL-6 TNF- alpha and IFN- gamma were not detected in significant 
15572176IL-6IL-61.6For example in the CNS interleukin-1_amp_#x3b2 (IL-1_amp_#x3b2;) IL-1_amp_#x3b2 and IL-6 exert a powerful regulation of glial cells 109 
15572176IL-6IL-61.6Proinflammatory IL-1_amp_#x3b2 and IL-6 are synthesized by neuroglia during epileptic activity 105 the response 
15572176IL-6IL-61.6with tumour necrosis factor-alpha (TNF-_amp_#x3b1;), TNF-_amp_#x3b1 IL-1_amp_#x3b2 and IFN_amp_#x3b3 induces IL-6 COX-2 and iNOS and makes the cells vulnerable to undergo 
15572176IL-6IL-61.6Activated astrocytes are potent producers of IL-6 
15572176IL-6IL-61.6While IL-6 can promote survival and protect neurons from degeneration it can 
15777251IL-6IL-61.5specific alterations of IFN-gamma and IL-12 variations of TNF and IL-6 were associated with PD 
15777251IL-6IL-61.5more acute neurodegenerative conditions such as stroke the effect of IL-6 gene G-174C polymorphism was different in males and females 
16104843HGFHGF1.8The activation of VEGFR-1 results in the paracrine release of HGF (hepatocyte hepatocyte growth factor IL-6 (interleukin-6) interleukin-6 and other hepatotrophic 
16104843IL-6IL-61.8in the paracrine release of HGF (hepatocyte hepatocyte growth factor IL-6 (interleukin-6) interleukin-6 and other hepatotrophic molecules by LSECs to the 
16380619IL-6IL-61.3The authors compared IL-6 and tumor necrosis factor alpha TNF-alpha levels in CSF and 
16380619IL-6IL-61.3Elevated IL-6 levels in ALS could correspond to a normal response to 
16380619IL-6IL-61.3phases of the disease while several costimulating cytokines (IL-1_amp_#223;, IL-1_amp_#223 IL-6 and chemokines act to potentiate its effects 
16380619IL-6IL-61.3However there were conflicting results either no difference in IL-6 TNF-alpha or IL-12 was found in patients with ALS and 
16380619IL-6IL-61.3ALS and healthy and inflammatory controls or elevated levels of IL-6 and IL-1_amp_#223 in the CSF spinal cords and sera of 
16380619IL-6IL-61.3Increased IL-6 levels were shown in pulmonary conditions such as obstructive sleep 
16380619IL-6IL-61.3hypoxemia in the regulation of cytokines by studying TNF-alpha and IL-6 in the sera and CSF of hypoxemic and normoxemic patients 
16380619IL-6IL-61.3IL-6 and TNF-alpha levels in CSF and sera were determined using 
16380619IL-6IL-61.3We found higher levels of IL-6 in CSF ( z = -2.7 p = 0.02 in 
16380619IL-6IL-61.3A correlation exists between Pao 2 and levels of CSF IL-6 ( p = 0.0001 r = -0.7 serum IL-6 ( 
16380619IL-6IL-61.3CSF IL-6 ( p = 0.0001 r = -0.7 serum IL-6 ( p = 0.007 r = -0.6 serum TNF-alpha ( 
16380619IL-6IL-61.3In neurologic controls we found higher levels of IL-6 in CSF ( z = -2.8 p = 0.02 in 
16380619IL-6IL-61.3There were correlations between Pao 2 and CSF IL-6 ( p = 0.01 r = 0.5 serum IL-6 ( 
16380619IL-6IL-61.3CSF IL-6 ( p = 0.01 r = 0.5 serum IL-6 ( p = 0.01 r = 0.5 and serum TNF-alpha 
16380619IL-6IL-61.3We found no correlation between IL-6 or TNF-alpha levels in plasma and those in CSF 
16380619IL-6IL-61.3IL-6 and TNF-alpha levels did not correlate with age clinical presentation 
16380619IL-6IL-61.3We found an increase in IL-6 levels in CSF and sera and TNF-alpha in sera in 
16380619IL-6IL-61.3A correlation existed between IL-6 levels and the severity of hypoxemia in both groups suggesting 
16380619IL-6IL-61.3hand hypoxia stimulates the proinflammatory cytokines such as TNF-alpha and IL-6 mediated by others transcriptional factors nuclear factor-kappaB AP-1 and SP-1 
16380619IL-6IL-61.3excitatory amino acid nitric oxide and proinflammatory cytokines such as IL-6 TNF-alpha and IL-1_amp_#223 
16380619IL-6IL-61.3Higher IL-6 and TNF-alpha levels could therefore correspond to a normal response 
16380619IL-6IL-61.3It was demonstrated that the upregulation of IL-6 induced by hypoxemia could represent an endogenous neuroprotective mechanism against 
16380619IL-6IL-61.3A neuroprotective effect of increased levels of IL-6 was also observed in animal models of ALS or in 
16380619IL-6IL-61.3Our findings suggest that increased levels of IL-6 TNF-alpha PGE-2 and COX-2 observed in patients with ALS parallel 
16380619IL-6IL-61.3This may explain the age-associated increase in IL-6 sera levels found after exercise in patients with neuromuscular diseases 
16436205IL-6IL-61.8IL-6 which has some neuroprotective functions 20 tended to decrease in 
16436205IL6IL61.8Most cytokines including TNF_amp_#x003b1 and IL6 that we find upregulated in primary glial cultures or in 
16510725IL-6IL-61.3detected in IL-12p35 IL-10 IL-18 IFN gamma or IFN beta IL-6 TGF-beta3 and LT alpha or LT beta (data data not 
16624536IL-6IL-61.6In response to secondary stimuli such as interleukin-1 (IL-1), IL-1 IL-6 and TNF- microglia exert maximal activity through secretion of inflammatory 
16624536IL-6IL-61.6IL-6 knockout mice not only fail to demonstrate the early microglial 
16624536IL-6IL-61.6reduced astrocytic response in keeping with a dual role of IL-6 in both mediating motor neuron/microglial neuron microglial and microglial/astrocytic microglial 
16624536IL-6IL-61.6microglia derived from adult mutant SOD1 transgenic mice show decreased IL-6 production in response to LPS-stimulated activation compared to controls 37 
16624536IL-6IL-61.6experiments fractalkine suppressed the production of nitric oxide (NO), NO IL-6 and TNF-by activated microglia and suppressed neuronal cell death induced 
16624536IL-6IL-61.6interactions include a number of pro-inflammatory cytokines (e.g., e.g. IL-1 IL-6 and TNF- 77 78 and 79 and neurotrophic factors (e.g., 
16624536IL-6IL-61.6that recruits the further secretion of pro-inflammatory cytokines (e.g., e.g. IL-6 IL-8 colony stimulating factors (CSFs), CSFs IFN- _amp_#x3b2 and can 
16624536IL-6IL-61.6neuronal apoptosis in vitro through a TNF-dependant mechanism whereas IL-3 IL-6 bFGF and M-CSF are ineffective in the same experimental paradigm 
16624536IL-6IL-61.6COX-2 114 and can produce proinflammatory mediators including prostaglandins 115 IL-6 116 and TNF- 114 
16647138IL-6IL-61.3of putative regulatory sites including the cyclic AMP response element IL-6 response element AP-2 nuclear factor-_amp_#x3ba B (NF-_amp_#x3ba;B), NF-_amp_#x3ba B Sp-1 
16753239IL-6IL-61.015d-PGJ 2 inhibited NO as well as the cytokines IL-1_amp_#x3b2 IL-6 and TNF-_amp_#x3b1 and the chemokine MCP-1 by both primary mouse 
16753239IL-6IL-61.015d-PGJ 2 inhibited LPS induction of NO TNF-_amp_#x3b1 IL-1_amp_#x3b2 and IL-6 in primary astrocytes 
16753239IL-6IL-61.0For example these PPAR-_amp_#x3b3 agonists blocked TNF-_amp_#x3b1 and IL-6 expression by monocytes 
16753239IL-6IL-61.0studies demonstrated that TZDs block the production of iNOS TNF-_amp_#x3b1 IL-6 and COX-2 by primary rat microglia and astrocytes and protected 
16753239IL-6IL-61.0of NO as well as the pro-inflammatory cytokines TNF-_amp_#x3b1 IL-1_amp_#x3b2 IL-6 IL-12 p40 and the chemokine MCP-1 by primary mouse microglia 
16753239IL-6IL-61.0retinoic acid suppressed microglial production of NO TNF-_amp_#x3b1 IL-1_amp_#x3b2 and IL-6 in an additive manner ( Xu et al. 2005 
16753239IL-6IL-61.0additive manner in inhibiting LPS induction of NO TNF-_amp_#x3b1 IL-1_amp_#x3b2 IL-6 and MCP-1 expression in primary astrocytes (unpublished unpublished data 
17018025IL-6IL-61.6shown to reduce the production of pro-inflammatory cytokines such as IL-6 IL-8 tumor necrosis factor-alpha (TNF-A), TNF-A MIP-1A and RANTES in 
17555556IL-6IL-61.0nitric oxide superoxide and pro-inflammatory cytokines including TNF-A IL-1B and IL-6 
17555556IL-6IL-61.0days mSOD1 G93A microglia produced significantly more TNF-A and less IL-6 than wild-type microglia after LPS treatment 
17569578IL-6IL-61.9TNF_amp_#x3b1 interferon _amp_#x3b3;_amp_#xa0;(IFN_amp_#x3b3;), _amp_#x3b3 _amp_#xa0 IFN_amp_#x3b3 and interleukin 6 (IL-6) IL-6 are regularly found in multiple sclerosis brain lesions and in 
17569578IL-6IL-61.9treated mice showed an impaired generation of IFN_amp_#x3b3 TNF_amp_#x3b1 and IL-6 in response to MOG peptide in vitro restimulation 
17582695IL-6IL-61.3neurodegenerative disorders such as ALS and PD e.g. IL-1beta and IL-6 32 
17597167IL-6IL-61.8The proinflammatory cytokines of which interleukin-1 (IL-1), IL-1 IL-6 and tumour necrosis factor-_amp_#x3b1 (TNF-_amp_#x3b1;) TNF-_amp_#x3b1 are involved in the 
17597167IL-6IL-61.8The levels of IL-1_amp_#x3b2 IL-6 and TNF-_amp_#x3b1 in different brain regions of the Tg hsIL-1ra 
17597167IL-6IL-61.8Experimental studies have shown the reciprocal interactions between cytokines IL-1 and IL-6 and APP/_amp_#x3b2;-amyloid APP _amp_#x3b2 -amyloid (A_amp_#x3b2;) A_amp_#x3b2 peptide 
17597167IL-6IL-61.8studies have shown the reciprocal interactions between cytokines IL-1 and IL-6 and APP/_amp_#x3b2;-amyloid APP _amp_#x3b2 -amyloid (A_amp_#x3b2;) A_amp_#x3b2 peptide 
17597167IL-6IL-61.8mouse models of AD exemplified by the early expression of IL-6 mRNA prior to the appearance of amyloid plaques in mice 
17597167IL-6IL-61.8between the levels of IL-1_amp_#x3b2 and those of IL-1ra and IL-6 respectively in response to KA changed over time in such 
18040778IL-6IL-61.6elicited robust amounts of several cytokines/chemokines, cytokines chemokines including TNF-A IL-6 IL-1B CCL2 CCL5 and CXCL10 
18246426IL-6IL-61.3a result of its anti-inflammatory action on cytokines such as IL-6 
18246426IL-6IL-61.3Moreau et al 29 measured IL-6 and TNF-A in patients with ALS 
18464925IL-6IL-61.6reported to inhibit the production of nitric oxide (NO), NO IL-6 and TNF-_amp_#x003b1 as well as expression of the inducible enzymes 
9562310il 6il 61.0we assayed il 6 in 105 cerebrospinal fluid csf samples from patients with als ms htlv 1 associated myelopathy ham and controls.  
9562310il 6il 61.0there was considerable overlap in il 6 levels in all patient groups.  
9562310il 6il 61.0the mean il 6 in 27 patients with als was significantly higher than in 21 patients in the other neurological disease ond group p=0.0075 .  
9562310il 6il 61.0overall csf il 6 correlated with protein concentration but not with percentage igg or igg albumin index.  
9562310il 6il 61.0patients with csf oligoclonal bands were no more likely to have detectable il 6 than patients without oligoclonal bands.  
9562310il 6il 61.0similarly il 6 did not correlate with clinical disease activity in ms when subgroups of patients were compared or when an individual patient was followed over time.  
9562310il 6il 61.0the elevated il 6 in als may reflect an ongoing humoral immune response or il 6 may be non specifically expressed in these patients as a putative neurotrophic factor in response to nerve cell degeneration.  
9562310il 6il 61.0il 6 is a b cell differentiation factor that was first described by hirano et al.  
9562310il 6il 61.0cerebrospinal fluid csf levels of il 6 are consistently elevated in herpes simplex virus encephalitis and other bacterial and viral cns infections houssiau et al. 1988 and frei et al. 1988 .  
9562310il 6il 61.0il 6 was detected in experimental allergic encephalomyelitis csf gijbels et al. 1990 and systemic lupus erythematosus with central nervous system involvement hirohata and miyamoto 1990 but il 6 was not detected in multiple sclerosis ms houssiau et al. 1988 ; frei et al. 1988 and araga et al. 1991 or detected no more frequently than in neurological disease controls hauser et al. 1990 .  
9562310il 6il 61.0reports of il 6 in non inflammatory cns disease prompted the present study of csf in patients with amyotrophic lateral sclerosis als .  
9562310il 6il 61.0we found a higher frequency of detection and higher levels of il 6 in als than in the other neurological disease control group.  
9562310il 6il 61.0in contrast there was no significant difference in csf il 6 in either ms or ham patients compared to other neurological disease controls and there was no correlation of csf immune parameters and il 6 levels.  
9562310il 6il 61.0these results are consistent with the hypothesis that csf il 6 in als has an non immune origin occurring as a neurotrophic response to nerve cell damage.  
9562310il 6il 61.0the il 6 dependent hybridoma cell line mh6obsf2 matsuda et al. 1988 was cloned four times.  
9562310il 6il 61.0without il 6 in the media no viable cells remained in this subclone by 72 h of culture.  
9562310il 6il 61.0il 6 was quantitated by reference to a dose calibration curve of recombinant human il 6 kindly supplied by drs hirano and kishimoto assayed with mh6obsf2 cells under the same conditions as the csf samples.  
9562310il 6il 61.0csf il 6 values were expressed as log 1 0 pg/ml.  
9562310il 6il 61.0the sensitivity of il 6 detection was determined to be 1.6 pg/ml.  
9562310il 6il 61.0specificity of the assay was confirmed by showing no mitogenic response with other recombinant human cytokines il 1 il 1_amp_#x3b2; il 2 tnf and abrogating the il 6 effect by anti il 6 polyclonal antibody genzyme boston ma .  
9562310il 6il 61.0because of the lower boundary of detectability of 1.6 pg/ml for the il 6 assay or log 1 0 il 6 of 0.2 non parametric techniques were used.  
9562310il 6il 61.0as shown in fig. 1 there was considerable overlap in il 6 levels in all patient groups.  
9562310il 6il 61.0table 2 shows il 6 detection in 78% of 27 patients with als median log 1 0 il 6 of 1.01 55% of 20 patients with ms median 0.94 59% of 17 patients with ham median 0.905 48% of 21 patients with other neurological diseases median 0.825 and 25% of the non neurological disease contro 
9562310il 6il 61.0analysis by the non parametric wilcoxon rank sum test showed a significant difference in csf il 6 between the als and ond group p =0.0075 but no significant difference between ms and ond p =0.55 or ham and the ond group p =0.47 .  
9562310il 6il 61.0the als ms and ham groups all had statistically significant higher mean il 6 levels than the non neurological disease control: p _amp_#x3c;0.0001 for the als group p =0.03 for the ms group and p =0.03 for the ham group.  
9562310il 6il 61.0the greatest csf il 6 level in the als group log 1 0 il 6 of 2.55 was a sample from the national neurological research bank.  
9562310il 6il 61.0although these results failed to show a higher mean il 6 level in patients with recognized immune mediated cns disease ms and ham groups this failure may be because of the relatively small number of patients in these groups.  
9562310il 6il 61.0to determine if il 6 varies with the activity of immune mediated disease data from the ms patients were analyzed depending on whether the disease was in clinical relapse or was stable or in remission.  
9562310il 6il 61.0the results in fig. 2 show no significant difference in csf il 6 levels with 7 of 12 patients in relapse having detectable il 6 compared to 4 of 8 patients with ms in remission or with stable disease.  
9562310il 6il 61.0despite these csf changes consistent with fluctuating immune mediated activity in the cns the csf il 6 levels remained at undetectable levels in all four spinal taps.  
9562310il 6il 61.0to evaluate further any correlation of csf il 6 with the extent of immune mediated activity in the cns csf parameters were compared in patients with and without detectable il 6.  
9562310il 6il 61.0there was a significantly higher total igg in ms patients with detectable il 6 levels not shown but this correlation was not seen in any of the other patient groups and did not hold when data were combined for all four groups.  
9562310il 6il 61.0similarly the percent igg was higher in the als group with detectable il 6 but not in the combined patient group not shown .  
9562310il 6il 61.0only total csf protein was significantly higher in patients with detectable il 6.  
9562310il 6il 61.0as shown in table 3 ; mean csf protein in patients with detectable il 6 was 49.0_amp_#xb1;3.8 compared to 33.2_amp_#xb1;3.0 in patients with undetectable il 6 p _amp_#x3c;0.01 .  
9562310il 6il 61.0fig. 4 shows csf il 6 levels in 35 patients with ms or ham who had either oligoclonal bands in the csf 14 patients or did not have oligoclonal bands 21 patients .  
9562310il 6il 61.0although the il 6 level was slightly higher in patients without oligoclonal bands and the percentage of detectable il 6 was higher 67% versus 43% these differences were not statistically significant.  
9562310il 6il 61.0we found a modest but statistically significant elevation of csf il 6 in als patients fig 1 .  
9562310il 6il 61.0in comparing these studies a similar percentage of als patients had undetectable csf il 6 6/27 versus 2/15 ; but 37% of our patients had il 6 levels greater than 10 pg/ml compared to only 7% in the published study.  
9562310il 6il 61.0the il 6 levels in als csf less than 0.96 log 10 pg/ml were considerably lower than levels we detected in 8 patients with herpes simplex encephalitis 1.76 log 1 0 pg/ml sekizawa unpublished .  
9562310il 6il 61.0nevertheless the modest il 6 elevation noted here may be related to an ongoing humoral immune response in some patients with als.  
9562310il 6il 61.0serum il 6 was not measured in als but prior studies have shown that il 6 can concentrate in the csf compartment e.g during active cns systemic lupus erythematosus hirohata and miyamoto 1990 .  
9562310il 6il 61.0il 6 along with tnf has been reported to be highly expressed in perivascular inflammatory cells around ms demyelinating plaques woodroofe and cuzner 1993 .  
9562310il 6il 61.0in spite of this expression we did not find a statistically significant elevation of il 6 in ms csf.  
9562310il 6il 61.0moreover we were unable to document an increase in il 6 during active disease both within a group of ms patients fig 2 and in a single patient followed over time fig 3 .  
9562310il 6il 61.0however inaccuracies in detecting active disease do not explain our inability and the inability of others araga et al. 1991 ; laurenzi et al. 1990 and maimone et al. 1991 to correlate il 6 and csf parameters of immune mediated disease including percentage igg and elevated igg albumin index table 3 .  
9562310il 6il 61.0the overall results in the ms and ham patients suggests either: i il 6 does not play a major role in these disease; or ii detection of il 6 is unreliable in the csf of immune mediated cns parenchymal disease because of instability or because il 6 from brain in these disease does not enter the csf compartment .  
9562310il 6il 61.0 is unreliable in the csf of immune mediated cns parenchymal disease because of instability or because il 6 from brain in these disease does not enter the csf compartment .  
9562310il 6il 61.0it is possible that the il 6 elevation in als is of non immune origin.  
9562310il 6il 61.0il 6 has been shown to induce neuronal differentiation satoh et al. 1988 and play a neurotrophic role hama et al. 1989 in tissue culture systems.  
9562310il 6il 61.0moreover il 6 has been shown to increase in brain in response to injury woodroofe et al. 1991 .  
9562310il 6il 61.0we speculate that il 6 may be produced by astrocytes or microglial cells in als as a non specific response to degeneration of motor neurons or other cns cells.  
9562310il 6il 61.0this non specific effect may explain the slightly higher levels of il 6 in ond controls compared to non neurological disease controls.  
9562310il 6il 61.0future studies of multiple cytokine expression in als and other neurological disease would be helpful to distinguish an immune versus a non immune origin of il 6.  
9562310il 6il 61.0csf il 6 levels in als ms including relapsing remitting and stable disease ham ond and non neurological disease control control groups with bars indicating the mean_amp_#xb1;standard error of the mean in each 
9562310il 6il 61.0csf il 6 levels in ms patients with either relapsing or remitting/stable disease with bars indicating the mean_amp_#xb1;standard error of the mean in the two patient groups.  
9562310il 6il 61.0csf il 6 levels in ms or ham patients that either have ocb+ or do not have ocb_amp_#x2212; oligoclonal bands in the csf.  
9562310interleukin 6interleukin 61.0interleukin 6|  
10525172il 6il 61.0microglial cells can be activated by pro inflammatory cytokines il 1 il 6 and tnf_amp_#x3b1; as well as by _amp_#x3b2; amyloid peptide _amp_#x3b2; a [ 82 90 ] the first 42 amino acids of amyloid precursor protein app fig 6 .  
11173059interleukin 6interleukin 61.0furthermore interleukin 2 interleukin 4 and interleukin 6 levels are elevated in the ventricular cerebrospinal fluid and in the caudate nucleus and putamen of patients with parkinson's disease hirsch 2000 .  
11173059interleukin 6interleukin 61.0in contrast the c allele of a variable number of tandem repeat polymorphism in the 3' flanking region of the interleukin 6 gene is associated with a delayed onset and a lower risk of alzheimer disease papassotiropoulos et al. 1999b .  
14511332il 6il 61.0levels of il 1beta il 6 and tumour necrosis factor alpha were found to be elevated in experimental and human sals ghezzi et al . 1998 ; sekizawa et al . 1998 ; li et al . 2000 .  
14511332il 6il 61.0cytokines could also contribute to high expression of cox 2 in sals particularly il 1beta and il 6.  
14511332il 6il 61.0il 1beta and il 6 are assumed to derive from glia.  
14511332il 6il 61.0recently one of us was able to show that the expression of cox 2 in crc parallels the expression of il 1 beta and il 6 in crc maihofner et al . 2003 .  
14597108interleukin 6interleukin 61.0ediators released from activated microglia which have harmful effects on neuron survival including peroxynitrite [ beal et al. 1997 and tohgi et al. 1999 ] prostaglandin e 2 [ almer et al. 2002 ] and interleukin 6 [ sekizawa et al. 1998 ] has been demonstrated in the cerebrospinal fluid and spinal cord of als patients for review see [ mcgeer and mcgeer 2002 ] .  
15081582il 6il 61.0microglia have different regulatory mechanisms than macrophages fibroblasts and synovial cells that can induce cox 2 via the cytokines tnf il 1_amp_#x3b2; and il 6.  
15453089il 6il 61.0in spite of the prominent microglial activation classical pro inflammatory mediators such as il 1 il 6 tnf [alpha] and ifn [gamma] were not detected in significant amount in a murine model of prion disease in which c57bl/6j mice are infected with scrapie the prion form affecting sheep.  
15572176il 6il 61.0for example in the cns interleukin 1_amp_#x3b2; il 1_amp_#x3b2; and il 6 exert a powerful regulation of glial cells [ 109 ].  
15572176il 6il 61.0proinflammatory il 1_amp_#x3b2; and il 6 are synthesized by neuroglia during epileptic activity [ 105 ] the response being greater when seizures are associated with neuronal damage suggesting the release of neuronal mediators.  
15572176il 6il 61.0activation of murine astrocytes with tumour necrosis factor alpha tnf _amp_#x3b1; il 1_amp_#x3b2; and ifn_amp_#x3b3; induces il 6 cox 2 and inos and makes the cells vulnerable to undergo apoptosis in response to fas ligand fasl [ 39 ].  
15572176il 6il 61.0activated astrocytes are potent producers of il 6.  
15572176il 6il 61.0while il 6 can promote survival and protect neurons from degeneration it can also promote astrocyte proliferation and activation [ 31 ].  
15777251il 6il 61.0indeed while ms patients and mice subjected to experimental autoimmune encephalomyelitis eae display gender specific alterations of ifn gamma and il 12 variations of tnf and il 6 were associated with pd.  
15777251il 6il 61.0also in case of more acute neurodegenerative conditions such as stroke the effect of il 6 gene g 174c polymorphism was different in males and females.  
16104843interleukin 6interleukin 61.0the activation of vegfr 1 results in the paracrine release of hgf hepatocyte growth factor il 6 interleukin 6 and other hepatotrophic molecules by lsecs to the extent that hepatocytes are stimulated to proliferate when co cultured with lsecs.  
16104843il 6il 61.0the activation of vegfr 1 results in the paracrine release of hgf hepatocyte growth factor il 6 interleukin 6 and other hepatotrophic molecules by lsecs to the extent that hepatocytes are stimulated to proliferate when co cultured with lsecs.  
16380619il 6il 61.0abnormal levels of interleukin il 6 were described in patients with als related to an inflammatory process.  
16380619il 6il 61.0the authors compared il 6 and tumor necrosis factor alpha tnf alpha levels in csf and sera from 10 hypoxemics and 10 normoxemics patients with als to those of 10 hypoxemics and 10 normoxemics neurologic controls.  
16380619il 6il 61.0elevated il 6 levels in als could correspond to a normal response to hypoxemia.  
16380619il 6il 61.0an excessive production of tumor necrosis factor alpha tnf alpha with lower csf levels of interleukin il 6 was demonstrated in a sod 1 mouse model suggesting an increase cytotoxic potential of microglia.  
16380619il 6il 61.0tnf alpha could act as a principal driver for neuroinflammation because its receptors are elevated in the presymptomatic phases of the disease while several costimulating cytokines il 1_amp_#223; il 6 and chemokines act to potentiate its effects.  
16380619il 6il 61.0however there were conflicting results: either no difference in il 6 tnf alpha or il 12 was found in patients with als and healthy and inflammatory controls or elevated levels of il 6 and il 1_amp_#223; in the csf spinal cords and sera of patients with als.  
16380619il 6il 61.0increased il 6 levels were shown in pulmonary conditions such as obstructive sleep apnea in which paroxystic nocturnal desaturations lead to chronic hypoxemia.  
16380619il 6il 61.0in light of the inflammatory hypothesis we investigated the role of hypoxemia in the regulation of cytokines by studying tnf alpha and il 6 in the sera and csf of hypoxemic and normoxemic patients with als and neurologic controls.  
16380619il 6il 61.0il 6 and tnf alpha levels in csf and sera were determined using a chemiluminescent assay quantiglo r_amp_d systems and an elisa test quantikine r_amp_d systems .  
16380619il 6il 61.0we found higher levels of il 6 in csf z = 2.7; p = 0.02 in serum z = 2.1; p = 0.04 and tnf alpha in serum z = 2.5; p = 0.01 in hypoxemic vs normoxemic patients with als figure 1 .  
16380619il 6il 61.0a correlation exists between pao 2 and levels of csf il 6 p = 0.0001 r = 0.7 serum il 6 p = 0.007 r = 0.6 serum tnf alpha p = 0.001 r = 0.7 in patients with als.  
16380619il 6il 61.0in neurologic controls we found higher levels of il 6 in csf z = 2.8; p = 0.02 in serum z = 2.3; p = 0.02 and tnf alpha in serum z = 2.0; p = 0.05 in hypoxemic controls vs normoxemic ones figure 2 .  
16380619il 6il 61.0there were correlations between pao 2 and csf il 6 p = 0.01 r = 0.5 serum il 6 p = 0.01 r = 0.5 and serum tnf alpha levels p = 0.01 r = 0.5 in neurologic controls.  
16380619il 6il 61.0we found no correlation between il 6 or tnf alpha levels in plasma and those in csf.  
16380619il 6il 61.0il 6 and tnf alpha levels did not correlate with age clinical presentation or disease duration.  
16380619il 6il 61.0we found an increase in il 6 levels in csf and sera and tnf alpha in sera in hypoxemic patients with als and hypoxemic neurologic controls vs normoxemic ones but no difference between patients with als and controls.  
16380619il 6il 61.0a correlation existed between il 6 levels and the severity of hypoxemia in both groups suggesting that cytokine levels must be interpreted according to the degree of hypoxemia.  
16380619il 6il 61.0on the other hand hypoxia stimulates the proinflammatory cytokines such as tnf alpha and il 6 mediated by others transcriptional factors: nuclear factor kappab ap 1 and sp 1.  
16380619il 6il 61.0cute hypoxemia episodes cause early microglia activation followed by the release of a variety of neurotoxic products including excitatory amino acid nitric oxide and proinflammatory cytokines such as il 6 tnf alpha and il 1_amp_#223;.  
16380619il 6il 61.0higher il 6 and tnf alpha levels could therefore correspond to a normal response to hypoxemia probably via nf kappab.  
16380619il 6il 61.0it was demonstrated that the upregulation of il 6 induced by hypoxemia could represent an endogenous neuroprotective mechanism against excitotoxic factor injury.  
16380619il 6il 61.0a neuroprotective effect of increased levels of il 6 was also observed in animal models of als or in the context of excitotoxicity after hypoxemia.  
16380619il 6il 61.0our findings suggest that increased levels of il 6 tnf alpha pge 2. and cox 2 observed in patients with als parallel motor neuronal loss and could correspond to a natural response to hypoxemia.  
16380619il 6il 61.0this may explain the age associated increase in il 6 sera levels found after exercise in patients with neuromuscular diseases including als.  
16380619interleukin 6interleukin 61.0csf and sera interleukin 6 levels and tumor necrosis factor alpha sera levels in patients with als according to the condition of hypoxemia or normoxemia pao 2 . *significant difference p _lt_ 0.05 between the hypoxemic and the 
16380619interleukin 6interleukin 61.0csf and sera interleukin 6 levels and tumor necrosis factor alpha sera levels in neurologic controls according to the condition of hypoxemia or normoxemia pao 2 . *significant difference p _lt_ 0.05 between the hypoxemic and t 
16436205il 6il 61.0il 6 which has some neuroprotective functions [ 20 ] tended to decrease in g93a sod1 cultures.  
16510725il 6il 61.0no changes were detected in il 12p35 il 10 il 18 ifn gamma or ifn beta il 6 tgf beta3 and lt alpha or lt beta data not shown .  
16624536il 6il 61.0in response to secondary stimuli such as interleukin 1 il 1 il 6 and tnf microglia exert maximal activity through secretion of inflammatory mediators fig 1 .  
16624536il 6il 61.0il 6 knockout mice not only fail to demonstrate the early microglial response to motor neuron injury but also show a reduced astrocytic response in keeping with a dual role of il 6 in both mediating motor neuron/microglial and microglial/astrocytic interactions [68] .  
16624536il 6il 61.0it is of interest that microglia derived from adult mutant sod1 transgenic mice show decreased il 6 production in response to lps stimulated activation compared to controls [37] .  
16624536il 6il 61.0in murine cell culture experiments fractalkine suppressed the production of nitric oxide no il 6 and tnf by activated microglia and suppressed neuronal cell death induced by microglia activated with lps and interferon gamma ifn _amp_#x3b3; in a dose dependent manner.  
16624536il 6il 61.0potential candidates for mediating microglia/motor neuron interactions include a number of pro inflammatory cytokines e.g. il 1 il 6 and tnf [77] [78] and [79] and neurotrophic factors e.g. plasminogen tgf _amp_#x3b2; bfgf bdnf ngf nt 3 and nt 4 [80] [81] and [82] .  
16624536il 6il 61.0il 1 mediates a general inflammatory response that recruits the further secretion of pro inflammatory cytokines e.g. il 6 il 8 colony stimulating factors csfs ifn /_amp_#x3b2; and can also have a trophic effect.  
16624536il 6il 61.0microglia can also inhibit sodium nitroprusside an no donor induced neuronal apoptosis in vitro through a tnf dependant mechanism whereas il 3 il 6 bfgf and m csf are ineffective in the same experimental paradigm [92] .  
16624536il 6il 61.0like microglia reactive astrocytes express inflammatory markers including inos and cox 2 [114] and can produce proinflammatory mediators including prostaglandins [115] il 6 [116] and tnf [114] .  
16647138il 6il 61.0the cox 2 gene also contains a number of putative regulatory sites including the cyclic amp response element il 6 response element ap 2 nuclear factor _amp_#x3ba;b nf _amp_#x3ba;b sp 1 pea 3 gata 1 and glucocorticoid response element wu 1995 .  
16647138il 6il 61.0the cox 1 gene also has some putative regulatory sites such as sp 1 ap 2 nf il 6 gata 1 and a shear stress response element but the location of these sites differs considerably from those in the cox 2 gene.  
16753239il 6il 61.0recently we demonstrated that thiazolidinediones which are commonly used to treat type ii diabetes and the naturally occurring 15d pgj 2 inhibited no as well as the cytokines il 1_amp_#x3b2; il 6 and tnf _amp_#x3b1; and the chemokine mcp 1 by both primary mouse microglia and astrocytes storer et al. 2005a and storer et al. 2005b .  
16753239il 6il 61.0 2004 demonstrated that the ppar _amp_#x3b3; agonist 15d pgj 2 inhibited lps induction of no tnf _amp_#x3b1; il 1_amp_#x3b2; and il 6 in primary astrocytes.  
16753239il 6il 61.0for example these ppar _amp_#x3b3; agonists blocked tnf _amp_#x3b1; and il 6 expression by monocytes.  
16753239il 6il 61.0recent studies demonstrated that tzds block the production of inos tnf _amp_#x3b1; il 6 and cox 2 by primary rat microglia and astrocytes and protected cortical neurons in a neuron glia co culture paradigm.  
16753239il 6il 61.0we recently demonstrated that a variety of ppar _amp_#x3b1; agonists inhibit the production of no as well as the pro inflammatory cytokines tnf _amp_#x3b1; il 1_amp_#x3b2; il 6 il 12 p40 and the chemokine mcp 1 by primary mouse microglia.  
16753239il 6il 61.0terestingly the ppar _amp_#x3b1; agonist fenofibrate in combination with the retinoid x receptor agonist 9 cis retinoic acid suppressed microglial production of no tnf _amp_#x3b1; il 1_amp_#x3b2; and il 6 in an additive manner xu et al. 2005 .  
16753239il 6il 61.0similarly fenofibrate and 9 cis ra acted in an additive manner in inhibiting lps induction of no tnf _amp_#x3b1; il 1_amp_#x3b2; il 6 and mcp 1 expression in primary astrocytes unpublished data .  
17018025il 6il 61.0il 4 has also been shown to reduce the production of pro inflammatory cytokines such as il 6 il 8 tumor necrosis factor alpha tnf a mip 1a and rantes in glial cultures treated with lipopolysaccharide or il 1 ledeboer et al 2000 ; ehrlich et al 1998 .  
17555556il 6il 61.0microglial activation can be associated with increased production of potentially cytotoxic substances such as nitric oxide superoxide and pro inflammatory cytokines including tnf a il 1b and il 6.  
17555556il 6il 61.0 2004 found that adult 60 days msod1 g93a microglia produced significantly more tnf a and less il 6 than wild type microglia after lps treatment.  
17569578interleukin 6interleukin 61.0several cytokines including tumor necrosis factor _amp_#x3b1;_amp_#xa0; tnf_amp_#x3b1; interferon _amp_#x3b3;_amp_#xa0; ifn_amp_#x3b3; and interleukin 6 il 6 are regularly found in multiple sclerosis brain lesions and in spinal cord infiltrates of eae mice [124] .  
17569578il 6il 61.0several cytokines including tumor necrosis factor _amp_#x3b1;_amp_#xa0; tnf_amp_#x3b1; interferon _amp_#x3b3;_amp_#xa0; ifn_amp_#x3b3; and interleukin 6 il 6 are regularly found in multiple sclerosis brain lesions and in spinal cord infiltrates of eae mice [124] .  
17569578il 6il 61.0in the same study splenocytes derived from wy14 643 treated mice showed an impaired generation of ifn_amp_#x3b3; tnf_amp_#x3b1; and il 6 in response to mog peptide in vitro restimulation.  
17582695il 6il 61.0biochemical mediators such as glutamate are modulated by certain cytokines in neurodegenerative disorders such as als and pd e.g. il 1beta and il 6 [32] .  
17597167il 6il 61.0the proinflammatory cytokines of which interleukin 1 il 1 il 6 and tumour necrosis factor _amp_#x3b1; tnf _amp_#x3b1; are involved in the initial immune response help to drive the elimination of pathogens and resolution of the inflammatory process.  
17597167il 6il 61.0the levels of il 1_amp_#x3b2; il 6 and tnf _amp_#x3b1; in different brain regions of the tg hsil 1ra mice were analysed in view of possible compensatory upregulation.  
17597167il 6il 61.0experimental studies have shown the reciprocal interactions between cytokines il 1 and il 6 and app/_amp_#x3b2; amyloid a_amp_#x3b2; peptide.  
17597167il 6il 61.0gliosis and an increased expression of proinflammatory cytokines are also found in the brain of transgenic mouse models of ad exemplified by the early expression of il 6 mrna prior to the appearance of amyloid plaques in mice with overexpression of human app with the so called swedish mutation [31] and gliosis in apolipoprotein apoe knock out mice [32] .  
17597167il 6il 61.0the ratios between the levels of il 1_amp_#x3b2; and those of il 1ra and il 6 respectively in response to ka changed over time in such a way as to indicate an imbalance at time points when the body temperature was altered [51] .  
18040778il 6il 61.0in these experiments m. tuberculosis infected microglia elicited robust amounts of several cytokines/chemokines including tnf a il 6 il 1b ccl2 ccl5 and cxcl10.  
18246426il 6il 61.0czlonkowska et al. [ 28 ] showed that neuroprotective activity of estrogen could be partially a result of its anti inflammatory action on cytokines such as il 6.  
18246426il 6il 61.0moreau et al. [ 29 ] measured il 6 and tnf a in patients with als.  
18436268interleukin 6interleukin 61.0it is suggested that hcy can enhance pro inflammatory cytokines production such as interleukin 6 tnf _amp_#x3b1; and c reactive protein holven et_amp_#xa0;al. 2006 .  
18464925il 6il 61.0the two tzd compounds np00111 and np01138 were reported to inhibit the production of nitric oxide no il 6 and tnf _amp_#x003b1; as well as expression of the inducible enzymes inos and cox2 induced in lps stimulated astrocyte and microglial cultures [ 58 ].