不同功能位点介导α干扰素的免疫调节和中枢镇痛作用

Distinct structural bases of the immunoregulatory and central analgesic effects of IFNα

细胞因子α干扰素 (IFNα)具有中枢镇痛作用。抗内源性阿片肽血清与IFNα能发生明显的交叉反应 ,提示IFNα与内源性阿片肽之间存在着共同的抗原决定基。采用基因定点突变技术 ,获得系列IFNα突变体 ,并分别测定其免疫学活性和镇痛能力。结果显示 ,IFNα突变体Y1 2 9S IFNα免疫学活性显著下降 ,但仍然保留了很强的镇痛能力 ,阿片受体拮抗剂纳洛酮能够阻断Y1 2 9S IFNα的镇痛作用。实验结果表明 ,IFNα分子存在着相互独立的免疫和镇痛两个功能位点 ,分别介导免疫调节作用和中枢镇痛作用。结果还提示 ,IFNα的免疫调节和中枢镇痛作用可能是由不同的受体途径介导的。

Interferon alpha (IFNα), a cytokine, is also an analgesic molecule. There is significant cross reactivity between IFNα and anti opioid sera, suggesting a strong antigenic relatedness between human IFNα molecules and opioid peptides. Different structural basis of the immunoactivity and analgesic effect of IFNα can be demonstrated by different reactivities of the two reactions towards different mutants of IFNα obtained by using the site directed mutagenesis. When the 129th Tyr residue of human IFNα was mutated to Ser, the immunoactivity of the mutant almost disappeared, while the strong analgesic activity still persisted, which could be blocked by naloxone. These results indicate that there exist distinct domains in the IFNα molecule, which mediate immune and analgesic effects differentially, and that the receptor mechanism underlying immune and analgesic effects of IFNα may be different.