INHIBITION OF HUMAN MONONUCLEAR CELL-PROLIFERATION, INTERLEUKIN SYNTHESIS, MESSENGER-RNA FOR IL-2, IL-6, AND LEUKOTRIENE-B(4) SYNTHESIS BY A LIPOXYGENASE INHIBITOR

Human peripheral blood mononuclear cells (PBMCs) were cultured in vitro with various stimuli and in the presence or absence of a 5-lipoxygenase (5-LO) inhibitor, A-63162, to measure its effects on PBMC proliferation, interleukin-2 receptor (IL-2R) expression, interleukin-2 (IL-2) synthesis, interleukin-6 (IL-6) synthesis, and accumulation of messenger RNA for IL-2 or IL-6. A-63162 inhibited PBMC proliferation stimulated by phytohemagglutinin (PHA) and phorbol myristate acetate (PMA) plus A23187, IL-2 receptor expression stimulated by PHA, and IL-2 or IL-6 synthesis induced by PHA plus PMA or PMA plus A23187. At the same concentration, A-63162 inhibited accumulation of mRNA for IL-2 or IL-6 and also inhibited leukotriene B4 (LTB4) synthesis. Our data indicate that the 5-LO inhibitor A-63162 has immunosuppressive activity that may be due to inhibition of LTB4 production or to direct inhibitory actions of A-63162 on IL-2 and IL-6 synthesis.