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.

In vitro effects of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-on e (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-1 beta from these cells stimulated with lipopolysaccharides (LPS) in a dose-dependent manner (0.3-30 micrograms/ml). The release of IL-6 from THP-1 cells, as determined 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 micrograms/ml, respectively. Northern blotting analysis using LPS-stimulated THP-1 cells indicated that the inhibitory effect of T-614 on IL-1 beta production is caused by the suppression of IL-1 beta mRNA expression. The inhibition of cytokine production by T-614 may provide an important insight into the additional mechanisms contributing to its antiinflammatory activities.