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.
Lee
J C
JC
Department of Immunology, Smith Kline & French Laboratories, Swedeland, PA 19479.
Votta
B
B
Griswold
D E
DE
Hanna
N
N
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D013189:SRS-A / Q000096:biosynthesis; D013844:Thiazoles / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007093:Imidazoles; D007375:Interleukin-1; D013189:SRS-A; D013844:Thiazoles; C052026:6-(4-fluorophenyl)-2,3-dihydro-5-(4-pyridinyl)imidazo(2,1-b)thiazole