Pharmacological Studies on 3-Formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one (T-614), a Novel Antiinflammatory Agent. 4th Communication : Inhibitory Effect on the Production of Interleukin-1 and Interleukin-6

Abstract

In vitro effects of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one (T-614), a novel antiinflammatory compound, on the production of interleukin-1 (IL-1) and/or interleukin-6 (IL-6) by human monocytes and the THP-1 cells of a human monocytic cell line, were examined. T-614 inhibited the release of immunoreactive IL-1β from these cells stimulated with lipopolysaccharides (LPS) in a dose-dependent manner (0.3-30 μg/ml). The release of IL-6 from THP-1 cells, as detrmined by the assays for its hepatocyte-stimulating activities and immunoreactivities, was inhibited by T-614 with the IC₅₀ values of 2.0 and 6.6 μg/ml, respectively. Northern blotting analysis using LPS-stimulated THP-1 cells indicated that the inhibitory effect of T-614 on IL-1β production is caused by the suppression of IL-1β mRNA expression. The inhibition of cytokine production by T-614 may provide an important insight into the additional mechanisms contributing to its antiinflammatory activities.