Inhibitory effect of SK&F 86002 on monocyte IL-1 production.

The effects of several anti-inflammatory and anti-arthritic drugs on the in vitro production of interleukin-1 by human monocytes were examined. SK&F 86002-A2 was shown to be a potent inhibitor of IL-1 production with a 50% inhibitory concentration (IC50) of 1.3 +/- 0.5 microM. Standard compounds which inhibit the cyclooxygenase (CO) or CO and 5-lipoxygenase (5LO) pathways of arachidonic acid metabolism did not inhibit IL-1 production at nontoxic concentrations. Analysis of SK&F 86002 analogs also showed no clear correlation between 5LO and IL-1 synthesis inhibitory activity. The precise mechanism of action is not known except that it is post-transcriptional. Thus, SK&F 86002 may serve as a useful reagent in the understanding of the synthetic, processing and/or secretory pathways of interleukin-1, and may provide important insight into the treatment of disease states where aberrant IL-1 production is implicated.