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

Lymphocytic choriomeningitis virus (LCMV) infection of beta2-microglobulin-deficient (beta2m-/-) mice results in a substantial loss of body weight that is not mediated by the virus itself, but rather by CD4+ T cells responding to the viral infection. In this study, we further characterized LCMV-induced weight loss in immunocompetent and beta32m-/- mice. We show that intracranial (i.c.), but not intraperitoneal (i.p.) LCMV infection elicited significant weight loss and that weight loss was preceded by anorexia. Also, 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 beta2m-/- mice. LCMV-infected female beta2m-/- mice also had significantly more interleukin (IL)-betag in their cerebrospinal fluid (CSF) than did male beta2m-/- mice. Finally, intracerebroventricular (i.c.v.) administration of anti-IL-1beta antibody, but not control immunoglobulin G (IgG), attenuated the initial weight loss and increased food intake. Taken together, these results suggest that the majority of weight loss after intracranial LCMV infection is the result of anorexia and IL-1beta mediates initial anorexic weight loss.