The Eft of Dual Inhibitor, Sk&F 86002, On Helper T Cell Functions

Publisher Website
Google Scholar
Abstract
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 mμm), the mixed lymphocyte response (IC50 = 16 mμM), and proliferation of antigen specific T cells (cloned line, IC50 = 11 mμM; uncloned line, IC50 = 13 mμM). 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 mμM), 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 inhibir 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.