|
Indomethacin is well known as a prostaglandin (PG) E₂ synthetase inhibitor, which has antipyretic and anti-inflammatory 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 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 interferon (IFN)-γ levels in supernatants, whereas indomethacin did not affect the LPS- increased levels of IL-2 and IFN-γ. These data, therefore, indicate that indomethacin may attenuate the pathogenesis of IL-1β, induced by LPS and maintain thetumoricidal cellular immune effects by LPS-increasee production of IL-2 and IFN-γ in tumor -bearing state.
|