The effect of dual inhibitor, SK&F 86002, on helper T cell functions.
SK&F 86002, a mixed cyclooxygenase-lipoxygenase inhibitor, was examined for its effects on helper T cell functions. The drug was found to inhibit concanavalin A-induced mitogenesis of splenic T cells (IC50 = 13 microns), the mixed lymphocyte response (IC50 = 16 microM), and proliferation of antigen specific T cells (cloned line, IC50 = 11 microM; uncloned line, IC50 = 13 microM). In contrast, another mixed cycloxygenase-lipoxygenase inhibitor, BW775c, did not have such effects at non-cytotoxic levels. These T cell functions are believed to be dependent on the effects of elaborated IL-1. SK&F 86002 has been shown to inhibit the production of mature IL-1 (IC50 = 1 microM), possibly accounting for the anti-inflammatory effects of the drug in rheumatoid arthritis models. In an in vivo model of contact sensitivity, SK&F 86002 was able to inhibit mouse footpad swelling, demonstrating additional anti-inflammatory activity. As an inhibitor of IL-1 synthesis or release, SK&F 86002 may be useful for the treatment of T cell-dependent inflammation.
Barton
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Department of Biological Sciences, Discovery Research, Allergan, Inc., Irvine, CA 92715.
James
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000941:Antigens; D003877:Dermatitis, Contact / Q000188:drug therapy; D004140:Dinitrophenols / Q000276:immunology; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008815:Mice, Inbred Strains; D012710:Serum Albumin, Bovine / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology; D013844:Thiazoles / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000941:Antigens; D004140:Dinitrophenols; D007093:Imidazoles; D007375:Interleukin-1; D013844:Thiazoles; C034638:dinitrophenyl-bovine serum albumin; D012710:Serum Albumin, Bovine; C052026:6-(4-fluorophenyl)-2,3-dihydro-5-(4-pyridinyl)imidazo(2,1-b)thiazole