Cytokine Inhibition by A Novel Steroid, Mometasone Furoate

Abstract

Mometasone furoate (9α, 21 dichloro-11β, 17α dihydroxy-16α methyl-1, 4 pregnadiene-3, 20 dione-17–[2′] furoate) was an unexpectedly potent inhibitor of the in vitro production of three inflammatory cytokines, IL-11, IL-6, and TNF-α. the potency of mometasone furoate in inhibiting cytokine production was compared to that of hydrocortisone, betamethasone, dexamethasone, and beclomethasone.

IL-6 and TNF-α were both produced by WEHI-265.1 (murine myelomonocytic leukemia) cells following stimulation by lipopolysaccharide (LPS). Twenty-four hours after stimulation by LPS, the cell-free supernatant fluids were removed. Their cytokine content was analyzed using ELISAs specific for each cytokine.

IL-1 synthesis was induced in the harvested peritoneal macrophages of BALB/c mice by incubation with LPS for twenty-four hours. the IL-1 content in the cell-free supernatant fluids was determined by the thymocyte-costimulator bioassay.

Using these systems, mometasone furoate was found to be the most potent steroid tested for inhibiting the production of the three cytokines. the IC50′s were 0.05 nM (IL-1), 0.15 nM (IL-6), and 0.25 nM (TNF-α). the inhibition of the production of proinflammatory mediators by extremely low concentrations of mometasone furoate suggests that this steroid should be highly effective in various disorders.