Herpes simplex virus type 2-induced mortality following genital infection is blocked by anti-tumor necrosis factor alpha antibody in CXCL10-deficient mice.

The role of tumor necrosis factor alpha (TNF-alpha) was evaluated for CXCL10-deficient (CXCL10(-/-)) mice which succumbed to genital herpes simplex virus type 2 (HSV-2) infection and possessed elevated levels of virus and TNF-alpha but not other cytokines in the central nervous system (CNS) and vaginal tissue within the first 7 days following virus exposure. Anti-TNF-alpha but not control antibody treatment offsets the elevated mortality rate of CXCL10(-/-) mice, despite increased CNS viral titers. In addition, TNF-alpha neutralization suppressed recruitment of leukocyte subpopulations into the CNS, which is associated with reduced CCL2 and CXCL9 expression. Collectively, the results implicate TNF-alpha as the principal mediator of mortality in response to genital HSV-2 infection.