白细胞介素18对白细胞介素1的胰岛损伤效应无调节作用

摘要

Objective　To investigate if there is any effect of interleukin-18 (IL-18) or if IL-18 modulates IL-1β effects on islet fun ction.Methods　Insulin release and nitrite production from isolated islets of newborn Wistar rats were measured after incubation with or w ithout cytokines.Reverse transcription polymerase chain reaction (RT-PCR) was u sed to detect mRNA expression of the IL-18 receptor signaling chain (IL-18Rβ) .Results　(1) There were no significant effects of 0.625～ 10nmol/L of recombinant murine (rm) IL-18 alone on accumulated or glucose-cha llenged insulin release and nitrite production after 24h.(2) 15pg/ml of recombi nant human (rh) IL-1β significantly increased nitrite production and inhibited insulin release.However,0.625～10nmol/L of rm IL-18 failed to modulate the abo ve effects caused by IL-1β.(3) 24h rm IL-12 preincubation failed to sensitize islets to the effects of 10nmol/L of rm or recombinant rat (rr) IL-18 alone or to pri me islets to IL-1β actions on insulin release and nitrite production.(4) IL-1 8Rβ mRNA was not expressed in isolated islets even after exposure to IL-12 for 48h.Conclusion　Unlike IL-1β,IL-18 dose not play a dir ect role in the destruction of islet β-cell function.%目的观察白细胞介素18(IL-18)对胰岛功能的效应、IL-18对IL-1β的胰岛损伤效应的影响。方法新生Wistar大鼠离体胰岛与细胞因子孵育后，观测胰岛素释放和亚硝酸盐的变化，并用逆转录-聚合酶链反应(RT-PCR)观察IL-18受体信号链(IL-18Rβ)mRNA的表达水平。结果 (1)0.625～10nmol/L基因重组小鼠(rm)IL-18孵育胰岛24h后，对累积的和葡萄糖刺激的胰岛素释放以及亚硝酸盐生成均无显著效应；(2)15pg/ml基因重组人(rh)IL-1β明显促进亚硝酸盐生成和抑制胰岛素释放，而0.625～10nmol/L rm IL-18则不影响IL-1β的上述效应；(3)rm IL-12预培养24h不能促使胰岛对10nmol/L rm或基因重组大鼠(rr)IL-18的反应性出现，也未使IL-18呈现加强IL-1β的上述效应；(4)离体胰岛即使与IL-12孵育48 h后，仍不见IL-18Rβ mRNA的表达。结论与IL-1β不同，IL-1 8在胰岛β细胞损伤中不发挥直接作用。