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The role of proinflammatory cytokines in wasting disease during lymphocytic choriomeningitis virus infection

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Kamperschroer, C and Quinn, Daniel (2002) The role of proinflammatory cytokines in wasting disease during lymphocytic choriomeningitis virus infection. JOURNAL OF IMMUNOLOGY, 169 (1). pp. 340-349. [Journal article]

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Abstract

Infection with pathogens often leads to loss of body weight, but the cause of weight loss during infection is poorly understood. We used the infection of mice with lymphocytic choriomeningitis virus (LCMV) as a model to study how pathogens induce weight loss. If LCMV is introduced into the CNS of CTL-deficient mice, the immune response against the virus leads to a severe weight loss called wasting disease. We planned to determine what components of this antiviral immune response mediate wasting disease. By adoptive transfer, we show that CD4 T cells activated by LCMV infection are sufficient to cause wasting disease. We examined the role of cytokines in LCMV-induced wasting disease using mice lacking specific cytokines or cytokine receptors. Results of adoptive transfer experiments suggest that TNF-alpha is not involved in LCMV-induced wasting disease and show that IFN-gamma contributes to the disease. Consistent with a role for IFN-gamma in wasting, we find that IFN-gamma is necessary for LCMV-specific CD4 T cell responses in the CNS, most likely because it is required to induce MHC class 11 expression. Our data also indicate that IL-1 is required for LCMV-induced wasting and that IL-6 contributes to the wasting disease. Additionally, our results identify a-melanocyte-stimulating hormone as a potential mediator of the disease. Overall, this work defines the critical role of virus-primed CD4 T cells and of proinflammatory cytokines in the pathogenesis of wasting disease induced by LCMV infection.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
ID Code:22897
Deposited By:Dr Daniel Quinn
Deposited On:31 Jul 2012 10:26
Last Modified:31 Jul 2012 10:26

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