Modulation of IL-1 inflammatory and immunomodulatory properties by IL-6.
Among the major cytokines present in inflammatory lesions interleukin-1 (IL-1), tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) share many biological activities. Since IL-1 alpha, IL-1 beta and TNF alpha have been previously demonstrated to play an important role in connective tissue destruction by stimulating the production of prostaglandin E2 (PGE2) and collagenase, these functions were investigated in the presence or absence of natural human IL-6 (nhIL-6) or recombinant human IL-6 (rhIL-6). IL-6 was found 1 degree to stimulate immunoglobulin A production by the CESS B cell line up to 19 fold without being affected by the presence of IL-1 beta and 2 degrees to stimulate murine thymocytes proliferation up to 2-4 fold, with an increase up to 60-fold in costimulation with either IL-1 alpha or beta. IL-6 alone, even at very high concentrations (up to 200 U/ml and 50 ng/ml), did not induce PGE2 production by fibroblasts and synovial cells. However, IL-1 alpha or beta induced PGE2 production by human dermal fibroblasts and by human synovial cells was inhibited (in 5/8 experiments) up to 62% by addition of IL-6. On the contrary in 2/4 experiments TNF alpha-induced PGE2 production was increased (approximately 2 fold) by the addition of IL-6. IL-1 and TNF alpha-induced collagenase production in synovial cells remained unchanged in the presence of IL-6.(ABSTRACT TRUNCATED AT 250 WORDS)
Hauptmann
B
B
Department of Medicine, Hôpital Cantonal Universitaire, Geneva, Switzerland.
Van Damme
J
J
Dayer
J M
JM
D000276:Adjuvants, Immunologic; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015232:Dinoprostone / Q000096:biosynthesis; D004347:Drug Interactions; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology; D007375:Interleukin-1 / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000008:administration & dosage*; D008213:Lymphocyte Activation; D051379:Mice; D003012:Microbial Collagenase / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D007071:Immunoglobulin A, Secretory; D007375:Interleukin-1; D015850:Interleukin-6; D003012:Microbial Collagenase; D015232:Dinoprostone