The effects of restraint stress on the neuropathogenesis of Theiler's virus infection II: NK cell function and cytokine levels in acute disease.

Psychological stress is thought to play an important role in multiple sclerosis. We have been investigating the role of restraint stress in Theiler's virus infection in mice as a model for multiple sclerosis. We have previously determined that restraint stressed CBA mice had higher levels of mortality following infection with Theiler's virus. We proposed that this was due to high levels of stress-induced corticosterone, which resulted in decreased numbers of circulating lymphocytes, decreased inflammatory cell infiltrates into the brain and consequently decreased viral clearance from the central nervous system (CNS). The effect of restraint stress on the innate immune response to Theiler's virus is further investigated in the current study. Restraint stressed mice developed clinical signs of encephalitis, thymic atrophy, and adrenal hypertrophy. Decreased numbers of circulating lymphocytes and increased numbers of neutrophils were observed in the stressed mice. Stressed mice also had lower numbers of spleen cells which correlated with the decreased numbers of lymphocytes in circulation. Restraint stress caused elevations in serum tumor necrosis alpha (TNF-alpha). Virus-induced natural killer cell (NK) cytotoxic activity was significantly reduced in restrained mice at one day post infection which may account for the reduced viral clearance from the CNS. These data suggest that stress-induced immunosuppression of cytolytic NK cell activity may account in part for the reduced ability to clear virus from the CNS and increased mortality observed in this model.