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. 1995 Jan;36(1):45–49. doi: 10.1136/gut.36.1.45

Soluble interleukin-6 receptors in inflammatory bowel disease: relation to circulating interleukin-6.

K Mitsuyama 1, A Toyonaga 1, E Sasaki 1, O Ishida 1, H Ikeda 1, O Tsuruta 1, K Harada 1, H Tateishi 1, T Nishiyama 1, K Tanikawa 1
PMCID: PMC1382351  PMID: 7890234

Abstract

The in vivo appearance of soluble interleukin (IL)-6 receptor (sIL-6R) in serum from patients with inflammatory bowel disease was examined using an enzyme linked immunosorbent assay (ELISA). The serum sIL-6R concentrations in patients with active disease (ulcerative colitis, 148.4 (5.1); Crohn's disease, 142.3 (9.3) ng/ml; mean (SEM)) were significantly raised compared with those in patients with inactive disease (ulcerative colitis, 116.2 (7.2); Crohn's disease, 114.3 (7.1) ng/ml), some other type of colitis (104.8 (11.6) ng/ml), or in normal subjects (107.3 (2.4) ng/ml). These differences were also seen in paired samples examined during both active and inactive phases. Additionally, serum sIL-6R and IL-6 concentrations correlated significantly with C-reactive protein levels in both ulcerative colitis and Crohn's disease patients (r = 0.23 and 0.56, respectively; p < 0.05 for both). Furthermore, gel filtration analysis of serum from these patients showed two major peaks of immunoreactive IL-6-one peak corresponding to free IL-6 and another peak to sIL-6R-bound IL-6-this was further confirmed by a luminescence sandwich ELISA. These results, together with its in vitro effects, indicate that natural sIL-6R may function as a powerful enhancer of the IL-6-dependent immune processes observed in inflammatory bowel disease.

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Selected References

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  1. Fernandez-Botran R. Soluble cytokine receptors: their role in immunoregulation. FASEB J. 1991 Aug;5(11):2567–2574. doi: 10.1096/fasebj.5.11.1868981. [DOI] [PubMed] [Google Scholar]
  2. Foxwell B. M., Barrett K., Feldmann M. Cytokine receptors: structure and signal transduction. Clin Exp Immunol. 1992 Nov;90(2):161–169. doi: 10.1111/j.1365-2249.1992.tb07922.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gross V., Andus T., Caesar I., Roth M., Schölmerich J. Evidence for continuous stimulation of interleukin-6 production in Crohn's disease. Gastroenterology. 1992 Feb;102(2):514–519. doi: 10.1016/0016-5085(92)90098-j. [DOI] [PubMed] [Google Scholar]
  4. Hirata Y., Taga T., Hibi M., Nakano N., Hirano T., Kishimoto T. Characterization of IL-6 receptor expression by monoclonal and polyclonal antibodies. J Immunol. 1989 Nov 1;143(9):2900–2906. [PubMed] [Google Scholar]
  5. Honda M., Kitamura K., Matsuda K., Yokota Y., Yamamoto N., Mitsuyasu R., Chermann J. C., Tokunaga T. Soluble IL-2 receptor in AIDS. Correlation of its serum level with the classification of HIV-induced diseases and its characterization. J Immunol. 1989 Jun 15;142(12):4248–4255. [PubMed] [Google Scholar]
  6. Honda M., Yamamoto S., Cheng M., Yasukawa K., Suzuki H., Saito T., Osugi Y., Tokunaga T., Kishimoto T. Human soluble IL-6 receptor: its detection and enhanced release by HIV infection. J Immunol. 1992 Apr 1;148(7):2175–2180. [PubMed] [Google Scholar]
  7. Isaacs K. L., Sartor R. B., Haskill S. Cytokine messenger RNA profiles in inflammatory bowel disease mucosa detected by polymerase chain reaction amplification. Gastroenterology. 1992 Nov;103(5):1587–1595. doi: 10.1016/0016-5085(92)91182-4. [DOI] [PubMed] [Google Scholar]
  8. Kishimoto T., Akira S., Taga T. Interleukin-6 and its receptor: a paradigm for cytokines. Science. 1992 Oct 23;258(5082):593–597. doi: 10.1126/science.1411569. [DOI] [PubMed] [Google Scholar]
  9. Kishimoto T. The biology of interleukin-6. Blood. 1989 Jul;74(1):1–10. [PubMed] [Google Scholar]
  10. LaMarre J., Wollenberg G. K., Gonias S. L., Hayes M. A. Cytokine binding and clearance properties of proteinase-activated alpha 2-macroglobulins. Lab Invest. 1991 Jul;65(1):3–14. [PubMed] [Google Scholar]
  11. Le J. M., Vilcek J. Interleukin 6: a multifunctional cytokine regulating immune reactions and the acute phase protein response. Lab Invest. 1989 Dec;61(6):588–602. [PubMed] [Google Scholar]
  12. Mackiewicz A., Rose-John S., Schooltink H., Laciak M., Górny A., Heinrich P. C. Soluble human interleukin-6-receptor modulates interleukin-6-dependent N-glycosylation of alpha 1-protease inhibitor secreted by HepG2 cells. FEBS Lett. 1992 Jul 20;306(2-3):257–261. doi: 10.1016/0014-5793(92)81012-b. [DOI] [PubMed] [Google Scholar]
  13. Mackiewicz A., Schooltink H., Heinrich P. C., Rose-John S. Complex of soluble human IL-6-receptor/IL-6 up-regulates expression of acute-phase proteins. J Immunol. 1992 Sep 15;149(6):2021–2027. [PubMed] [Google Scholar]
  14. Mahida Y. R., Kurlac L., Gallagher A., Hawkey C. J. High circulating concentrations of interleukin-6 in active Crohn's disease but not ulcerative colitis. Gut. 1991 Dec;32(12):1531–1534. doi: 10.1136/gut.32.12.1531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Matsuda T., Hirano T., Nagasawa S., Kishimoto T. Identification of alpha 2-macroglobulin as a carrier protein for IL-6. J Immunol. 1989 Jan 1;142(1):148–152. [PubMed] [Google Scholar]
  16. Mitsuyama K., Sasaki E., Toyonaga A., Ikeda H., Tsuruta O., Irie A., Arima N., Oriishi T., Harada K., Fujisaki K. Colonic mucosal interleukin-6 in inflammatory bowel disease. Digestion. 1991;50(2):104–111. doi: 10.1159/000200747. [DOI] [PubMed] [Google Scholar]
  17. Mueller C., Knoflach P., Zielinski C. C. T-cell activation in Crohn's disease. Increased levels of soluble interleukin-2 receptor in serum and in supernatants of stimulated peripheral blood mononuclear cells. Gastroenterology. 1990 Mar;98(3):639–646. [PubMed] [Google Scholar]
  18. Myren J., Bouchier I. A., Watkinson G., Softley A., Clamp S. E., de Dombal F. T. The O.M.G.E. Multinational Inflammatory Bowel Disease Survey 1976-1982. A further report on 2,657 cases. Scand J Gastroenterol Suppl. 1984;95:1–27. [PubMed] [Google Scholar]
  19. Nakajima T., Yamamoto S., Cheng M., Yasukawa K., Hirano T., Kishimoto T., Tokunaga T., Honda M. Soluble interleukin-6 receptor is released from receptor-bearing cell lines in vitro. Jpn J Cancer Res. 1992 Apr;83(4):373–378. doi: 10.1111/j.1349-7006.1992.tb00117.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Novick D., Engelmann H., Wallach D., Rubinstein M. Soluble cytokine receptors are present in normal human urine. J Exp Med. 1989 Oct 1;170(4):1409–1414. doi: 10.1084/jem.170.4.1409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rubin L. A., Nelson D. L. The soluble interleukin-2 receptor: biology, function, and clinical application. Ann Intern Med. 1990 Oct 15;113(8):619–627. doi: 10.7326/0003-4819-113-8-619. [DOI] [PubMed] [Google Scholar]
  22. Seckinger P., Isaaz S., Dayer J. M. Purification and biologic characterization of a specific tumor necrosis factor alpha inhibitor. J Biol Chem. 1989 Jul 15;264(20):11966–11973. [PubMed] [Google Scholar]
  23. Stevens C., Walz G., Singaram C., Lipman M. L., Zanker B., Muggia A., Antonioli D., Peppercorn M. A., Strom T. B. Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 expression in inflammatory bowel disease. Dig Dis Sci. 1992 Jun;37(6):818–826. doi: 10.1007/BF01300378. [DOI] [PubMed] [Google Scholar]
  24. TRUELOVE S. C., WITTS L. J. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br Med J. 1955 Oct 29;2(4947):1041–1048. doi: 10.1136/bmj.2.4947.1041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Taga T., Hibi M., Hirata Y., Yamasaki K., Yasukawa K., Matsuda T., Hirano T., Kishimoto T. Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell. 1989 Aug 11;58(3):573–581. doi: 10.1016/0092-8674(89)90438-8. [DOI] [PubMed] [Google Scholar]
  26. Taga T., Hibi M., Murakami M., Saito M., Yawata H., Narazaki M., Hirata Y., Sugita T., Yasukawa K., Hirano T. Interleukin-6 receptor and signals. Chem Immunol. 1992;51:181–204. [PubMed] [Google Scholar]
  27. Takemura H., Suzuki H., Yoshizaki K., Ogata A., Yuhara T., Akama T., Yamane K., Kashiwagi H. Anti-interleukin-6 autoantibodies in rheumatic diseases. Increased frequency in the sera of patients with systemic sclerosis. Arthritis Rheum. 1992 Aug;35(8):940–943. doi: 10.1002/art.1780350814. [DOI] [PubMed] [Google Scholar]
  28. Yasukawa K., Futatsugi K., Saito T., Yawata H., Narazaki M., Suzuki H., Taga T., Kishimoto T. Association of recombinant soluble IL-6-signal transducer, gp130, with a complex of IL 6 and soluble IL-6 receptor, and establishment of an ELISA for soluble gp130. Immunol Lett. 1992 Feb;31(2):123–130. doi: 10.1016/0165-2478(92)90138-e. [DOI] [PubMed] [Google Scholar]
  29. Yasukawa K., Saito T., Fukunaga T., Sekimori Y., Koishihara Y., Fukui H., Ohsugi Y., Matsuda T., Yawata H., Hirano T. Purification and characterization of soluble human IL-6 receptor expressed in CHO cells. J Biochem. 1990 Oct;108(4):673–676. doi: 10.1093/oxfordjournals.jbchem.a123261. [DOI] [PubMed] [Google Scholar]

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