Role of opioids for the microglial activation

有许多证据表明中枢神经系统（CNS）与免疫系统之间存在相互作用。小胶质细胞在中枢神经系统中发挥着重要的免疫功能，研究其与星形胶质细胞的相互作用是阐明其功能的重要途径。我们研究了各种阿片类药物和其他化合物对LPS诱导的培养的小胶质细胞和星形胶质细胞产生NO的影响。阿片类药物的作用因细胞制剂而异，表明内源性阿片类药物可能释放到培养基中，其程度在细胞培养条件下各不相同。我们研究了阿片类拮抗剂纳洛酮的作用。纳洛酮剂量依赖性地抑制小胶质细胞NO生成，但不抑制星形胶质细胞。甲硫氨酸脑啡肽可明显逆转这种抑制作用，β-内啡肽可轻微逆转这种抑制作用，而膜渗透性类似物二丁酰cAMP和黄嘌呤类似物propentofilline则有非常有趣的作用。它们对LPS诱导的NO和IL-6的产生几乎没有影响，但它们强烈抑制LPS诱导的TNF-α和IL-1β的产生。细胞因子产生的差异抑制表明，可能的控制小胶质细胞活化保护神经元损伤。进一步的研究可能会提供一个有益的工具，对神经退行性中枢疾病。

There are many evidences indicating the interaction between central nervous system (CNS) and immune system. Microglia play major roles of immunological function in CNS and it is a very important approaches to elucidate their function including the interaction to astrocytes. We examined the effects of various opioids and the other compounds on the LPS-induced NO production from cultured microglia and astrocytes. The effect of opioids varied from cell preparations to preparations suggesting that endogenous opioids may be released into culture media and its extent varies under cell culture conditions. We examined the effect of naloxone, an opioid antagonist. Naloxone inhibited dose-dependently NO production from microglia but not from astrocytes. The inhibition was reversed by Met-enkephalin remarkably and β-endorphin slightly.Among the other compounds examined, very interesting effects were observed in dibutyryl-cAMP, a membrane permeable analog, and propentofilline, a xanthine analoge. They showed almost no effect on LPS-induced production of NO and IL-6 ; however, they strongly inhibited LPS-induced production of TNF-α and IL-1β. The differential inhibition of cytokines production suggests that a possible control of microglial activation protects neuronal damage. Further investigation may provide a beneficial tool against neurodegenerative central diseases.