Inhibition of interleukin-1 release by IX 207-887.
Compound IX 207-887 is a novel antiarthritic agent which inhibits the release of interleukin-1 (IL-1) from human monocytes and mouse peritoneal macrophages in vitro at concentrations which are achieved therapeutically in human rheumatoid arthritis and in animal models of arthritis. In the present studies IL-1 activity in conditioned media, homogenates or lysates was monitored using four independent assay systems. Biologically active IL-1 was determined by, a) the induction of latent metalloproteinase-release from rabbit articular chondrocytes, which is relatively specific for IL-1 and b) by a sensitive thymocyte proliferation assay. Immunoreactive IL-1-beta was assayed by RIA and ELISA. In all test systems IX 207-887 significantly reduced both biologically active and immunoreactive IL-1 in culture media, whereas the levels of IL-1 in homogenates or lysates were either unaffected or only marginally reduced. The release of other monokines tested, such as interleukin-6 and tumour necrosis factor-alpha, and the secretion of lysozyme were only marginally influenced. IX 207-887 neither affected the adherence of human monocytes nor markedly inhibited IL-1 or IL-2-induced thymocyte proliferation. In the chondrocyte test no IL-1 antagonistic activity of IX 207-887 could be observed. All of these data indicate that IX 207-887 has the novel property of being an inhibitor of IL-1 release.
Schnyder
J
J
Sandoz Research Institute Berne Ltd., Switzerland.
Bollinger
P
P
Payne
T
T
D000818:Animals; D001681:Biological Assay; D001790:Blood Physiological Phenomena; D002356:Cartilage / Q000166:cytology / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000502:physiology; D003470:Culture Media; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007376:Interleukin-2 / Q000502:physiology; D015850:Interleukin-6 / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009113:Muramidase / Q000378:metabolism; D011863:Radioimmunoassay; D013876:Thiophenes / Q000494:pharmacology*; D013950:Thymus Gland / Q000166:cytology
D003470:Culture Media; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D013876:Thiophenes; C061029:IX 207-887; D007770:L-Lactate Dehydrogenase; D009113:Muramidase