不同功能位点介导α干扰素的免疫调节和中枢镇痛作用

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Ｙ１２９Ｓ－ＩＦＮα免疫学活性显著下降,但仍然保留了很强的镇痛能力,阿片受体拮抗纳洛酮能够阻断Ｙ１２９Ｓ－ＩＦＮα的镇痛作用。实验结果表明,ＩＦＮ

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

Interferon-alpha (IFNalpha), a cytokine, is also an analgesic molecule. There is significant cross reactivity between IFNalpha and anti-opioid sera, suggesting a strong antigenic relatedness between human IFNalpha molecules and opioid peptides. Different structural basis of the immunoactivity and analgesic effect of IFNalpha can be demonstrated by different reactivities of the two reactions towards different mutants of IFNalpha obtained by using the site-directed mutagenesis. When the 129th Tyr residue of human IFNalpha 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 IFNalpha molecule, which mediate immune and analgesic effects differentially, and that the receptor mechanism underlying immune and analgesic effects of IFNalpha may be different.