Role of histamine in natural killer cell-dependent protection against herpes simplex virus type 2 infection in mice.

Depletion of natural killer (NK) cells in vivo with anti-NK1.1 monoclonal antibody or anti-asialo-GM1 antiserum drastically reduced survival time in Swiss albino mice infected intravenously (i.v.) with herpes simplex virus type 2 (HSV-2). In contrast, depletion of NK cells did not affect the survival time of mice inoculated with HSV-2 by the intraperitoneal route. A single dose of histamine prolonged survival time in animals inoculated with HSV-2 i.v. but not in animals infected intraperitoneally. Treatment with the histamine H2 receptor antagonist ranitidine alone reduced survival time in i.v.-infected animals and blocked the protective effect of histamine. Histamine or ranitidine did not affect survival time in anti-NK1.1- or anti-asialo-GM1-treated animals. Our data suggest a role for histaminergic mechanisms in NK cell-mediated protection against HSV-2.