Dengue virus-induced cytotoxin releases nitrite by spleen cells

Dengue type-2 virus (DV) infection in mice induces T cells to produce a cytokine, the cytotoxic factor (CF), which induces H2-A positive macrophages to produce another cytokine, cyotoxin (CF2), which amplifies its cytotoxic effects on target cells. 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 CF2. Maximum NO2- production occurred at 1 hour after inoculation of 100 mu g CF2. Pretreatment of CF2 with anti-CF2-antisera (CF2-As) inhibited the production of NO2-. Pretreatment of the spleen cells with N-G-monomethyl-L-arginine (NMA) or with arginase inhibited NO2- production. The NO2- production was diminished in a dose dependent manner by treatment of spleen cells with the Ca2+ channel blocking drug, nifedipine and Zn2+ as ZnSO4. The findings of the present study thus demonstrate that CF2 induces production of NO2- in the spleen cells in a CA(2+)-dependent manner which may be a mechanism of target cell killing.