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

Interleukin-18 dose not modulate interleukin-1 toxic effects on rat islet 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) m RNA的表达水平。结果 (1) 0 .6 2 5～ 10 nmol/L 基因重组小鼠 (rm) IL- 18孵育胰岛 2 4h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 ) 15 pg/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 .6 2 5～ 10 nmol/L rm IL- 18则不影响 IL- 1β的上述效应 ;(3) rm IL- 12预培养 2 4h不能促使胰岛对 10 nmol/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 48h后 ,仍不见 IL- 18Rβ m RNA的表达。结论 与 IL- 1β不同 ,IL- 18在胰岛

Objective To investigate if there is any effect of interleukin-18 (IL-18) or if IL-18 modulates IL-1β effects on islet function.Methods Insulin release and nitrite production from isolated islets of newborn Wistar rats were measured after incubation with or without cytokines.Reverse transcription polymerase chain reaction (RT-PCR) was used 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-challenged insulin release and nitrite production after 24h.(2) 15pg/ml of recombinant 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 above 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 prime islets to IL-1β actions on insulin release and nitrite production.(4) IL-18Rβ 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 direct role in the destruction of islet β-cell function.