ROLE OF INTERFERON-GAMMA IN THE PATHOGENESIS OF LCMV-INDUCED MENINGITIS - UNIMPAIRED LEUKOCYTE RECRUITMENT, BUT DEFICIENT MACROPHAGE ACTIVATION IN INTERFERON-GAMMA KNOCK-OUT MICE

Generally, interferon-gamma (LFN-gamma) is considered a critical regul ator of T cell mediated inflammation. For this reason, we investigated the pathogenesis of lymphocytic choriomeningits in mice with a target ed defect of the gene encoding this cytokine. Our results revealed tha t IFN-gamma is redundant in the afferent phase of the antiviral T cell response as well as a local mediator of this T cell mediated inflamma tory disease. However, IFN-gamma may play an indirect role as it is in volved in reducing extraneural infection that may compete with CNS for available effector cells. Analysis of the inflammatory exudate disclo sed that leucocyte recruitment was unimpaired in the absence of IFN-ga mma as was the upregulation of ICAM-1 and VCAM-1 on endothelium at the inflammatory site. However, local macrophage activation (production o f tumor necrosis-alpha and NO) was significantly impaired. Notably, a viral peptide could also elicit a T cell mediated inflammatory respons e in virus-primed IFN-gamma knock-out mice, indicating that redundancy of this cytokine as a proinflammatory mediator is not restricted to i nflammatory reactions triggered by an active infection. Thus, T cell m ediated inflammation may be induced in the absence of IFN-gamma and lo cal macrophage activation. (C) 1998 Elsevier Science B.V. All rights r eserved.