INHIBITION OF INTERLEUKIN-1 SYNTHESIS BY TENIDAP - A NEW DRUG FOR ARTHRITIS

Tenidap is a new antiarthritic drug of novel chemical structure. This study shows the effects of tenidap on the in vitro synthesis of interleukin 1 (IL-1). IL-1 production by murine peritoneal macrophages was induced either by stimulation with lipopolysaccharide (LPS) or by phagocytosis of zymosan. With either stimulus, tenidap inhibited IL-1 production as measured by a quantitative competitive IL-1 receptor binding assay. Approximately 20 ng/mL of IL-1 was produced by 106 macrophages in response to LPS and about half that amount was produced in response to zymosan. Fifty percent inhibition of IL-1 production by tenidap was found of 3 μM for both stimuli. Using goat anti-1L-1α and Western blot analysis, the appearance of intracellular 34 kDA pro-IL-1α was inhibited by tenidap down to 3 μM. Tenidap decreased [35S]Met incorporation into cellular protein at 30 μM but not at 10 or 3 μM, indicating selectivity for IL-1 inhibition relative to total protein synthesis. Because tenidap inhibited IL-1 induction by both zymosan and LPS, it must act subsequently to receptor triggering. As the appearance of IL-1 was inhibited both intracellularly and extracellularly, the primary drug effect cannot be on secretion. © 1991.