암유발 생쥐에서 리포폴리사카라이드에 의해 유도된 사이토카인 생산에 미치는 인도메타신의 영향

Effect of Indomethacin on the Lipopolysaccharide-induced Production of Cytokines in Tumor-bearing Mice

Indomethacin is well known as a prostaglandin (PG) E2 synthetase inhibitor which has antipyretic and anti-in1ammatory effects and reduces the risk of cancer Growing tumors greatly induce hypersensitive responses to lipopolysaccharide (LPS). Thus, this study was investigated the effect of indomethacin at the on the LPS-induced production of cytokines in sarcoma-bearing ICR mice. Indomethacin at doses of 5mg/kg was administered orally 30 minutes before I.p. injection of LPS (8 mg/kg) 5 times for 7 days. LPS remarkedly increased tumor necrosis factor (TNF)- α And interleukin (IL)- 1β, levels in both serum and splenic supernatants compared with those in controls, while indomethacin significantly reduced the LPS-increased levels of IL-1β, in both serum and supernatants. LPS significantly enhanced IL-2 levels in serum and inter- feron (IFN)-γ levels in supernatants, whereas indomethacin did not affect the LPS- increased levels of IL-2 and IFN-. These data, therefore, indicate that indomethacin may attenuate the pathogenesis of IL-1β, induced by LPS and maintain the tumoricidal cellular immune effects by LPS-γincreasee production of IL-2 and IFN-γ in tumor -bearin g state.