Effect of SK&F 86002 on cytokine production by human monocytes

Human monocytes respond to a variety of stimuli in vitro by producing a number of physiologically important macromolecules including the cytokines. SK&F 86002, a dual inhibitor of the arachidonate metabolism, has been shown to inhibit LPS induced IL-1 production in human monocytes. We examined its effect on the production of other cytokines which are coordinately expressed as a result of LPS stimulation such as tumor necrosis factor alpha (TNF), alpha interferon (IFN-A), interferon beta-2 (IL-6) and granulocyte colony stimulating factor (g-CSF). The IC50 of SK&F 86002 for the TNF production was 5-8 microM, and greater than 20 microM for the other three cytokines. These IC50s were significantly higher than that previously reported for IL-1 production (1-2 microM). Taken together these data indicate that the inhibitory effect of SK&F 86002 on IL-1 production is selective and the production of cytokines in drug treated monocytes can be differentially affected.