Selective inhibition of human glial inducible nitric oxide synthase by interferon-β: Implications for multiple sclerosis

Nitric oxide generated from the inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of multiple sclerosis. Because significant species- and cell-specific differences exist in the expression of iNOS, we used primary human glial cell cultures to screen for an inhibitor of iNOS expression. Remarkably, among numerous soluble factors tested, interferon-β (IFN-β) alone showed a selective and potent inhibition of interleukin-1β/interferon-γ (IL-1β/IFN-γ)-induced iNOS expression in astrocytes. Inhibition of iNOS may provide a mechanism by which IFN-β can ameliorate inflammation and cytotoxicity in the central nervous system of patients with multiple sclerosis.