ABSENCE OF MODULATION OF MONOKINE PRODUCTION VIA ENDOGENOUS CYCLOOXYGENASE OR 5-LIPOXYGENASE METABOLITES - MK-886 (3-[1-(4-CHLOROBENZYL)-3-TERT-BUTYL-THIO-5-ISOPROPYLINDOL-2-YL]-2,2-DIMETHYLPROPANOIC ACID), INDOMETHACIN, OR ARACHIDONATE FAIL TO ALTER IMMUNOREACTIVE INTERLEUKIN-1-BETA, OR TNF-ALPHA PRODUCTION BY HUMAN MONOCYTES INVITRO

Human peripheral blood monocytes exposed to MK-886 (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2-dimethylpropanoic acid) at doses which abolish formation of 5-lipoxygenase metabolites showed unaltered interleukin-1β (IL-1β) or tumor necrosis factor-α (TNF-α) levels in response to phorbol ester, concanavalin A, serum-treated zymosan, or lipopolysaccharide. Indomethacin (10 μM), alone or in combination with MK-886, also failed to modulate monokine production in response to any stimulus. Exogenous arachidonate (3-30 μM) which augmented the formation of PGE2 and LTB4 in the absence of stimulation, also had no effect on monokine production. LPS-induced IL-1 and TNF production occurred despite stimulation of PGE2 synthesis. The results make a role for endogenous prostaglandins and leukotrienes in the regulation of monocyte IL-1β and TNF-α production unlikely. These data also indicate that MK-886, a novel inhibitor of 5-lipoxygenase product formation, is a potentially useful leukotriene inhibitor which does not affect monokine production. © 1991.