The role of interferon‐gamma in the pathogenesis of experimental autoimmune disease of the peripheral nervous system

Abstract

The role of interferon‐gamma in the pathogenesis of experimental autoimmune disease of the peripheral nervous system was investigated. Administration of rat recombinant interferon‐gamma markedly augmented both myelin‐induced and T‐cell line‐mediated experimental autoimmune neuritis. Conversely, in vivo application of a monoclonal antibody to interferon‐gamma suppressed the disease. Clinical and electrophysiological findings were corroborated by semiquantitative morphometric analysis. Mechanisms responsible for the enhancing effects of interferon‐gamma include upregulation of major histocompatibility complex class II antigen expression in the nerve lesion, increased cellular influx of T cells and macrophages, and heightened macrophage activity with enhanced release of toxic oxygen species. These observations establish a pivotal role of the cytokine interferon‐gamma in the pathogenesis of experimental autoimmune disease of the peripheral nervous system.