Immunopathologic weight loss in intracranial LCMV infection initiated by the anorexigenic effects of IL-1 beta

Lymphocytic choriomeningitis virus (LCMV) infection of beta(2)-microglobuli n-deficient (beta(2)m-/-) mice results in a substantial loss of body weight that is not mediated by the virus itself, but rather by CD4(+) T cells res ponding to the viral infection. In this study, we further characterized LCM V-induced weight loss in immunocompetent and beta(2)m-/- mice. We show that intracranial (i.c.), but not intraperitoneal (i.p.) LCMV infection elicite d significant weight loss and that weight loss was preceded by anorexia, Al so, uninfected mice fed an equivalent amount as eaten by infected mice had similar weight loss compared to their infected counterparts. Interestingly, both weight loss and anorexia were greater in female than male beta(2)m-/- mice. LCMV-infected female beta(2)m-/- mice also had significantly more in terleukin (IL)-1 beta in their cerebrospinal fluid (CSF) than did male beta (2)m-/- mice. Finally, intracerebroventricular (i.c.v.) administration of a nti-IL-1 beta antibody, but not control immunoglobulin G (IgG), attenuated the initial weight loss and increased food intake. Taken together, these re sults suggest that the majority of weight loss after intracranial LCMV infe ction is the result of anorexia and IL-1 beta mediates initial anorexic wei ght loss.