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.
Tanaka
K
K
Research Laboratories, Toyama Chemical Co., Ltd., Japan.
Aikawa
Y
Y
Kawasaki
H
H
Asaoka
K
K
Inaba
T
T
Yoshida
C
C
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D002460:Cell Line; D004347:Drug Interactions; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D007938:Leukemia / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001578:Benzopyrans; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D013449:Sulfonamides; C077313:T 614; D007213:Indomethacin