Relationship of functional and antigenic interleukin 6 to disease activity in inflammatory bowel disease

Hyams, Jeffrey S.; Fitzgerald, John E.; Treem, William R.; Wyzga, Nancy; Kreutzer, Donald L.

doi:10.1016/0016-5085(93)90336-b

Cited by 142 publications

(88 citation statements)

References 30 publications

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“…Among the known cytokines, a prominent role for interleukin (IL)-6 in this disease has been described extensively. Previous studies have shown that the serum levels of IL-6 increased in patients with active IBD and decreased after successful treatment [3][4][5][6][7]. The IL-6 levels also correlated with the severity and extent of disease [3,7].…”

Section: Introductionmentioning

confidence: 69%

A form of circulating interleukin-6 receptor component soluble gp130 as a potential interleukin-6 inhibitor in inflammatory bowel disease

Mitsuyama

Tomiyasu

Suzuki

et al. 2005

Clinical and Experimental Immunology

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SummaryThe presence and the role of soluble gp130, the soluble form of a component of the interleukin (IL)-6 receptor complex, were investigated in inflammatory bowel disease. The serum concentrations of soluble gp130 were increased in ulcerative colitis (active disease, median, 93·5 ng/ml; interquartile range, 26-125 ng/ml; inactive disease, 81 ng/ml, 24·8-137·3 ng/ml) and to a lesser extent in Crohn's disease (active disease, 66 ng/ml, 44·4-87·6 ng/ml; inactive disease, 63 ng/ml, 43·5-82·5 ng/ml) compared to normal controls (43 ng/ml, 27-59 ng/ml). Paired analysis of serum samples showed a decrease of IL-6 and soluble IL-6 receptor concentrations in both diseases and an increase of soluble gp130 concentrations, especially in ulcerative colitis, just after the resolution of disease exacerbation. Size fractionation of the serum revealed that a part of the IL-6 co-eluted with soluble gp130 and soluble IL-6 receptor. The IL-6-induced proliferation of murine B9 hybridoma was enhanced by recombinant soluble IL-6 receptor, whereas the proliferation was inhibited by recombinant soluble gp130. These results indicate that soluble gp130 may function as a natural inhibitor of the IL-6 actions in inflammatory bowel disease.

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Section: Introductionmentioning

confidence: 69%

A form of circulating interleukin-6 receptor component soluble gp130 as a potential interleukin-6 inhibitor in inflammatory bowel disease

Mitsuyama

Tomiyasu

Suzuki

et al. 2005

Clinical and Experimental Immunology

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“…IL-6 serum levels correlate with disease activity of both, CD and UC, and upon antiinflammatory treatment, IL-6 serum levels decline correlating to the decrease in disease activity [36,37]. The induction of C-reactive protein (CRP) is the liver is mediated by IL-6.…”

Section: Anti Interleukin-6 Strategiesmentioning

confidence: 99%

Review: New Anti-Cytokines for IBD: What is in the Pipeline?

Scharl

Vavricka²,

Rogler

2013

CDT

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Significant advances have been achieved in the understanding of the pathogenesis of inflammatory bowel disease (IBD). A number of susceptibility genes have been detected by large genome wide screening-approaches. New therapeutic concepts emerge from these insights. The most important progress in recent years certainly is the introduction of biologics in the therapy of IBD. TNF blockers have been shown to be very effective for the control of complicated disease courses. Currently, in addition to the three already established anti-TNF antibodies, new anti-TNF molecules, for example Golimumab, are in clinical trials and also reveal promising results. However, not all of the patients respond to anti-TNF treatment and many patients lose their response. Therefore, additional therapeutic approaches are urgently needed. Attractive therapy targets are cytokines as well as their receptors and signaling pathways. At the moment a large number of biologicals and inhibitors are tested in clinical trials and some of them provide very promising results for the treatment of IBD patients. In particular, inhibition of IL-12p40 by specific antibodies as well as of the janus kinase (JAK)3 by a small molecule promise to be very effective approaches. Though antibodies targeting for example IL-6, IL-6R, IL-13 or CCR9 are only in the early steps of clinical development, they have already demonstrated to be a possible treatment option which needs to be confirmed in further trials. Taken together a large number of new therapeutic anti-cytokine approaches are currently tested in clinical trials in IBD patients. In this review, the new therapeutic approaches for cytokine inhibition in IBD patients are discussed. Taken together a large number of new therapeutic anti-cytokine approaches are currently tested in clinical trials in IBD patients. In this review, the new therapeutic approaches for cytokine inhibition in IBD patients are discussed.

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“…Interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) are proinflammatory cytokines mainly produced by activated macrophages [8,9]. The production of these cytokines by lamina propria mononuclear cells is increased in Crohn's disease [10,11] and their serum level has been shown to be also increased and to be higher in active than in inactive disease [12][13][14][15]. Soluble TNF receptors (sTNFR) p55 and p75 are shed during expression of TNF receptor by various cells [16].…”

Section: Introductionmentioning

confidence: 99%

A high serum concentration of interleukin-6 is predictive of relapse in quiescent Crohn??s disease

Louis

Bélaïche

Kemseke

et al. 1997

European Journal of Gastroenterology & Hepatology

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Background/aims: Relapses of Crohn's disease are difficult to predict. We assessed the value of serum level of interleukin-6, tumour necrosis factor alpha (TNF-α) and soluble TNF receptors as predictors of relapse in quiescent Crohn's disease.Patients/methods: Thirty-six patients with inactive Crohn's disease, treated or not, were included. Various clinical and biological parameters, including interleukin-6, TNF-α and soluble TNF receptors serum levels were measured at inclusion in the study and the patients were followed clinically for 1 year. The relapse was defined as a Crohn's Disease Activity Index (CDAI) greater than 150 with an increase greater than 100 compared to the inclusion value. We analysed the ability of these parameters to predict relapse in parallel to clinical characteristics and other laboratory parameters.Results: Among the 32 variables tested, interleukin-6 serum level had the greatest ability to predict the time-torelapse, with 17-fold chance of relapse over a 1-year period for patients with an interleukin-6 serum level greater than 20 pg/ml than for patients with a lower level (P < 0.001). A high serum level of the soluble TNF receptors pS5 and p75 also had significant predictive value, in contrast to TNF-α serum levels. An interleukin-6 serum level greater than 20 pg/ml and either an acid α-1-glycoprotein level greater than 1.1 g/l or a soluble interleukin-2 receptor serum level greater than 95 pM/l were risk factors selected by a stepwise multivariate analysis. In both models a good prognosis group was defined by the absence of the two risk factors, a bad prognostic group by the presence of the two risk factors and an intermediate in between. With both models, the good prognosis group included 17 patients who experienced no relapse over the 1-year follow-up, whereas all patients (seven with the first model and six with the second) in the bad prognosis group had a relapse during the follow-up. Looking specifically at two homogeneous subgroups including either naturally/5-aminosalicylic acid (5-ASA) quiescent or corticoid quiescent patients, a very good predictive value for interleukin-6 serum concentration was also found.Conclusion: Interleukin-6 serum level alone or in association with other biological parameters such as acid α-1-glycoprotein or the soluble interleukin-2 receptor serum level may be useful for predicting the course of the disease in patients with quiescent Crohn's disease.

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Relationship of functional and antigenic interleukin 6 to disease activity in inflammatory bowel disease

Cited by 142 publications

References 30 publications

A form of circulating interleukin-6 receptor component soluble gp130 as a potential interleukin-6 inhibitor in inflammatory bowel disease

A form of circulating interleukin-6 receptor component soluble gp130 as a potential interleukin-6 inhibitor in inflammatory bowel disease

Review: New Anti-Cytokines for IBD: What is in the Pipeline?

A high serum concentration of interleukin-6 is predictive of relapse in quiescent Crohn??s disease

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