Interferons and autoimmunity

Autoimmunity can be accelerated in several genetically prone murine models and can even be induced in normal mice by treatment with interferon (IFN) or IFN-inducers. Several cases of IFN-induced autoimmune disease in humans also have been observed; however, more striking is the fact that some of the clinical manifestations in autoimmune diseases and many of the immunological aberrations can be mediated or enhanced by IFN. The finding of high levels of circulating IFN in many patients may be highly significant in that respect, and the characterization of the predominant type of IFN as an unusual acid-labile IFN-alpha may indicate an infectious etiologic agent in autoimmunity, since this peculiar IFN was mostly associated with viral infections in vivo or in vitro. The induction of MHC class II antigens on previously HLA-DR or Ia negative cells appears to be caused primarily by IFN-gamma and may have a central role in the pathogenesis of autoimmunity in susceptible individuals. Such aberrant HLA-DR expression on nonlymphoid cells can be detected early in the disease in the target organs of many varied autoimmune conditions and may trigger a cascade of self-directed, uncontrolled immune response in conjunction with other factors.