Immunoregulatory properties of novel specific inhibitors of 5-lipoxygenase

Abstract

The immunoregulatory properties of novel specific inhibitors of 5-lipoxygenase (5-LO) were investigated in vitro. These novel acetohydroxamic acids were found to inhibit the proliferation of lymphocytes in response to Interleukin-1 (IL-1) and Interleukin-2 (IL-2). Mitogen- and antigen-induced lymphoproliferation were likewise inhibited and so too was the spontaneous proliferation of transformed cells of myeloid and lymphoid origin. In this respect the compounds were one-tenth as potent as azathioprine on a molar basis. The production of IL-1 and IL-2 remained unaffected. Inhibition of lymphocyte proliferation was not related to inhibition of 5-LO. The latter occurred at 40-fold lower concentrations of 5-LO inhibitor. Moreover, inhibition of lymphoproliferation was not reversible in the presence of excess arachidonic acid. IL-1-induced collagenase production by chondrocytes was unaffected by 5-LO inhibitors. Contrary to a number of published reports, products of 5-LO do not appear to be obligatory mediators in IL-1 and IL-2 signal transduction. The immunosuppressive action of the 5-LO inhibitors described here seems to be a novel secondary property of the compounds.