Distinct domains of IFNα mediate immune and analgesic effects respectively


      Interferon-alpha (IFNα) is not only an immunoregulatory factor, but is also an analgesic molecule. The analgesic effect of IFNα was mediated by μ opioid receptor. After the 129th Tyr residue of human IFNα was mutated to Ser, the antiviral activity almost disappeared, but there still remained a strong analgesic activity that could be blocked by naloxone. These results indicate that there exist distinct domains in the IFNα molecule, which mediate immune and analgesic effects respectively, and suggest that there are different receptor mechanisms inducing immune and analgesic effects of IFNα. However, although the antiviral activity of IFNα decreased to 34.1% of wild type IFNα after the 122nd Tyr residue was changed to Ser, the analgesic activity of this mutant was lost completely. There were significant cross reactivities between INFα and anti-opioid sera. These studies show strong structural and functional similarities between INFα and opioid peptides, and inferred that the analgesic domain locates around the 122nd Tyr residue of IFNα molecule in tertiary structure.


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