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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1994 Mar;95(3):525–529. doi: 10.1111/j.1365-2249.1994.tb07030.x

Induction of autoimmune disease by graft-versus-host reaction across MHC class II difference: modification of the lesions in IL-6 transgenic mice

T Kimura, K Suzuki, S Inada, A Hayashi, H Saito, T Miyai, Y Ohsugi, Y Matsuzaki, N Tanaka, T Osuga, M Fujiwara
PMCID: PMC1535069  PMID: 8137550

Abstract

We examined the effect of IL-6 on the development of autoimmune diseases (primary biliary cirrhosis, Sjögren's syndrome) employing murine graft-versus-host reaction (GVHR) model with MHC class II disparity. For this purpose, we used IL-6 transgenic (B6.6) mice in which a high level of IL-6 was detected. C57B1/6 (B6) spleen T cells were injected into B6.6 mated with B6.C-H-2bm12 (bm12) mutant mice ((bm12×B6.6)F1) and GVHR with MHC class II disparity was induced. The transgenic hybrid mice with GVHR showed a larger spleen index and contained a higher serum level of IL-6 than those without GVHR. Autoimmune-like lesions in transgenic recipients became weakened compared with those in non-transgenic (bm12×B6)F1 recipients. In contrast, levels of antimitochondrial antibodies in (bm12×B6.6)F1 GVHR group were significantly higher than that of (bm12×B6)F1 GVHR group. These results indicate that IL-6 excessively produced in vivo might regulate the progression of autoimmune diseases.

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  1. Aderka D., Le J. M., Vilcek J. IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice. J Immunol. 1989 Dec 1;143(11):3517–3523. [PubMed] [Google Scholar]
  2. Berg P. A., Klein R., Lindenborn-Fotinos J. Antimitochondrial antibodies in primary biliary cirrhosis. J Hepatol. 1986;2(1):123–131. doi: 10.1016/s0168-8278(86)80015-0. [DOI] [PubMed] [Google Scholar]
  3. Epstein O., Thomas H. C., Sherlock S. Primary biliary cirrhosis is a dry gland syndrome with features of chronic graft-versus-host disease. Lancet. 1980 May 31;1(8179):1166–1168. doi: 10.1016/s0140-6736(80)91621-9. [DOI] [PubMed] [Google Scholar]
  4. Gauldie J., Richards C., Harnish D., Lansdorp P., Baumann H. Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7251–7255. doi: 10.1073/pnas.84.20.7251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Heseltine L., Turner I. B., Fussey S. P., Kelly P. J., James O. F., Yeaman S. J., Bassendine M. F. Primary biliary cirrhosis. Quantitation of autoantibodies to purified mitochondrial enzymes and correlation with disease progression. Gastroenterology. 1990 Dec;99(6):1786–1792. doi: 10.1016/0016-5085(90)90488-m. [DOI] [PubMed] [Google Scholar]
  6. Hirano T., Akira S., Taga T., Kishimoto T. Biological and clinical aspects of interleukin 6. Immunol Today. 1990 Dec;11(12):443–449. doi: 10.1016/0167-5699(90)90173-7. [DOI] [PubMed] [Google Scholar]
  7. Hirano T., Matsuda T., Turner M., Miyasaka N., Buchan G., Tang B., Sato K., Shimizu M., Maini R., Feldmann M. Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. Eur J Immunol. 1988 Nov;18(11):1797–1801. doi: 10.1002/eji.1830181122. [DOI] [PubMed] [Google Scholar]
  8. Houssiau F. A., Devogelaer J. P., Van Damme J., de Deuxchaisnes C. N., Van Snick J. Interleukin-6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides. Arthritis Rheum. 1988 Jun;31(6):784–788. doi: 10.1002/art.1780310614. [DOI] [PubMed] [Google Scholar]
  9. Kakumu S., Shinagawa T., Ishikawa T., Yoshioka K., Wakita T., Ito Y., Takayanagi M., Ida N. Serum interleukin 6 levels in patients with chronic hepatitis B. Am J Gastroenterol. 1991 Dec;86(12):1804–1808. [PubMed] [Google Scholar]
  10. Kohase M., Henriksen-DeStefano D., May L. T., Vilcek J., Sehgal P. B. Induction of beta 2-interferon by tumor necrosis factor: a homeostatic mechanism in the control of cell proliferation. Cell. 1986 Jun 6;45(5):659–666. doi: 10.1016/0092-8674(86)90780-4. [DOI] [PubMed] [Google Scholar]
  11. Lew W., Oppenheim J. J., Matsushima K. Analysis of the suppression of IL-1 alpha and IL-1 beta production in human peripheral blood mononuclear adherent cells by a glucocorticoid hormone. J Immunol. 1988 Mar 15;140(6):1895–1902. [PubMed] [Google Scholar]
  12. Matsuda T., Hirano T., Kishimoto T. Establishment of an interleukin 6 (IL 6)/B cell stimulatory factor 2-dependent cell line and preparation of anti-IL 6 monoclonal antibodies. Eur J Immunol. 1988 Jun;18(6):951–956. doi: 10.1002/eji.1830180618. [DOI] [PubMed] [Google Scholar]
  13. Mihara M., Ikuta M., Koishihara Y., Ohsugi Y. Interleukin 6 inhibits delayed-type hypersensitivity and the development of adjuvant arthritis. Eur J Immunol. 1991 Oct;21(10):2327–2331. doi: 10.1002/eji.1830211006. [DOI] [PubMed] [Google Scholar]
  14. Mihara M., Koishihara Y., Fukui H., Yasukawa K., Ohsugi Y. Murine anti-human IL-6 monoclonal antibody prolongs the half-life in circulating blood and thus prolongs the bioactivity of human IL-6 in mice. Immunology. 1991 Sep;74(1):55–59. [PMC free article] [PubMed] [Google Scholar]
  15. Muraguchi A., Hirano T., Tang B., Matsuda T., Horii Y., Nakajima K., Kishimoto T. The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells. J Exp Med. 1988 Feb 1;167(2):332–344. doi: 10.1084/jem.167.2.332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Okada M., Kitahara M., Kishimoto S., Matsuda T., Hirano T., Kishimoto T. IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells. J Immunol. 1988 Sep 1;141(5):1543–1549. [PubMed] [Google Scholar]
  17. Saitoh T., Fujiwara M., Nomoto M., Kamimura T., Ishihara K., Asakura H. Histologic studies on the hepatic lesions induced by graft-versus-host reaction in MHC class II disparate hosts compared with primary biliary cirrhosis. Am J Pathol. 1989 Aug;135(2):301–307. [PMC free article] [PubMed] [Google Scholar]
  18. Saitoh T., Fujiwara M., Nomoto M., Makino M., Watanabe H., Ishihara K., Kamimura T., Ichida F. Hepatic lesions induced by graft-versus-host reaction across MHC class II antigens: an implication for animal model of primary biliary cirrhosis. Clin Immunol Immunopathol. 1988 Oct;49(1):166–172. doi: 10.1016/0090-1229(88)90106-7. [DOI] [PubMed] [Google Scholar]
  19. Saitoh T., Ikarashi Y., Ito S., Watanabe H., Fujiwara M., Asakura H. Depletion of CD8+ cells exacerbates organ-specific autoimmune diseases induced by CD4+ T cells in semiallogeneic hosts with MHC class II disparity. J Immunol. 1990 Nov 15;145(10):3268–3275. [PubMed] [Google Scholar]
  20. Sheron N., Bird G., Goka J., Alexander G., Williams R. Elevated plasma interleukin-6 and increased severity and mortality in alcoholic hepatitis. Clin Exp Immunol. 1991 Jun;84(3):449–453. [PMC free article] [PubMed] [Google Scholar]
  21. Suematsu S., Matsusaka T., Matsuda T., Ohno S., Miyazaki J., Yamamura K., Hirano T., Kishimoto T. Generation of plasmacytomas with the chromosomal translocation t(12;15) in interleukin 6 transgenic mice. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):232–235. doi: 10.1073/pnas.89.1.232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Tang B., Matsuda T., Akira S., Nagata N., Ikehara S., Hirano T., Kishimoto T. Age-associated increase in interleukin 6 in MRL/lpr mice. Int Immunol. 1991 Mar;3(3):273–278. doi: 10.1093/intimm/3.3.273. [DOI] [PubMed] [Google Scholar]
  23. Tilg H., Wilmer A., Vogel W., Herold M., Nölchen B., Judmaier G., Huber C. Serum levels of cytokines in chronic liver diseases. Gastroenterology. 1992 Jul;103(1):264–274. doi: 10.1016/0016-5085(92)91122-k. [DOI] [PubMed] [Google Scholar]
  24. Van de Water J., Cooper A., Surh C. D., Coppel R., Danner D., Ansari A., Dickson R., Gershwin M. E. Detection of autoantibodies to recombinant mitochondrial proteins in patients with primary biliary cirrhosis. N Engl J Med. 1989 May 25;320(21):1377–1380. doi: 10.1056/NEJM198905253202104. [DOI] [PubMed] [Google Scholar]
  25. Woloski B. M., Smith E. M., Meyer W. J., 3rd, Fuller G. M., Blalock J. E. Corticotropin-releasing activity of monokines. Science. 1985 Nov 29;230(4729):1035–1037. doi: 10.1126/science.2997929. [DOI] [PubMed] [Google Scholar]

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