과량의 아연에 노출된 생쥐의 사이토카인 생산에 미치는 인도메타신의 영향

Effects of Idomethacin on the Production of Cytokines in Mice Exposed to Excessive Zinc

Zinc plays an important role in immunobiological responses, while excessive Binc attenuates immune aulctions in a dose-dependent manner Zinc excess has been reported to increase levels of plasma prostaglandin I s (PGE2), which is known to inhibit production of Th (helper T) 1-associated cytokines and to induce inf1ammatory responses. Thus, this study was investigated the effects of indomethacin, a potent inhibitor of PGE2 synthesis, on the proinf1ammatory cytosine and Iymphokine production in ICR mice exposed to excessive zinc. Indomethacin at doses of 5 mg/kg was administered I.p. 30 minutes before zinc chloride (Zn) 30 mg/kg orally daily for 10 days. Excessive Zn remarkedly increased tumor necrosis factor (TNF)-α and interleukin (IL)-1β Levels in both serum and splenic supernatants compared with those in ontrols, while indomethacin significantly reduced the excessive Zn-induced levels of IL-1β. In serum, excessive Zn significantly decreased the levels of IL-2 and interferon (IFN)-γ compared with those in controls, whereas indomethacin significantly enhanced the excessive Zn-decreased levels of IFN-γ but did not affect the Zn-decreased levels of serum IL-2. In splenic supernatants, All of excessive Zn, indomethacin, and combination of Zn and indomethacin significantly enhanced IL-2 levels compared with those in controls, but indomethacin didn't affect the Zn-induced production of IL-2. These data, therefore, suggest that indomethacin significantly attenuated the in vivo and ex vivo IL-lβ production increased by excessive zinc and remarkedly enhanced the in vivo excessive zinc-suppressed production of IFN- γbut not IL-2.