• dengue virus;
  • cytotoxic factor;
  • nitrite;
  • cytotoxicity

Dengue type 2 virus (DV) infection induces production of a cytokine, the cytotoxic factor (CF) in the spleen of mice. The present study was undertaken to investigate the production of nitrite (NO2) by the spleen cells of mice in vitro and in vivo following inoculation of DV or CF. Maximum NO2 production occurred at 45 min after inoculation of 5 μg CF, both in vitro and in vivo. The NO2 was produced by macrophages and T cells and not by B cells. Pretreatment of CF with anti-CF antisera inhibited production of NO2. DV-stimulated spleen cell culture supernatants showed peak production of CF and NO2 at 72 h. In DV-infected mouse spleen, maximum NO2 production occurred at 8–11 days post-infection, which correlated with peak cytotoxic activity in the spleen. Pretreatment of spleen cells with NG-monomethyl l-arginine (NMMA) inhibited NO2 production. NO2 production was abrogated in a dose-dependent manner by treatment of spleen cells with Ca2+ channel blocking drug, Nifedipine. The findings demonstrate that DV-induced CF induces production of NO2 in spleen cells, probably in a Ca2+-dependent manner, and may be a mechanism of target cell killing.