Production of nitrite by dengue virus-induced cytotoxic factor

Abstract

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 (NO⁻₂) by the spleen cells of mice in vitro and in vivo following inoculation of DV or CF. Maximum NO⁻₂ production occurred at 45 min after inoculation of 5 μg CF, both in vitro and in vivo. The NO⁻₂ was produced by macrophages and T cells and not by B cells. Pretreatment of CF with anti-CF antisera inhibited production of NO⁻₂. DV-stimulated spleen cell culture supernatants showed peak production of CF and NO⁻₂ at 72 h. In DV-infected mouse spleen, maximum NO⁻₂ production occurred at 8–11 days post-infection, which correlated with peak cytotoxic activity in the spleen. Pretreatment of spleen cells with N^G-monomethyl l-arginine (NMMA) inhibited NO⁻₂ production. NO⁻₂ 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 NO⁻₂ in spleen cells, probably in a Ca²⁺-dependent manner, and may be a mechanism of target cell killing.

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