Divergent roles of IFNs in the sensitization to endotoxin shock by lactate dehydrogenase-elevating virus

Abstract

The effect of mouse infection with lactate dehydrogenase-elevating virus (LDV), a usually non-pathogenic virus, on concomitant bacterial endotoxin shock was analyzed, in terms of lethality and cytokine production. A strong enhancement of susceptibility to the shock was observed in mice acutely infected with this virus. It correlated with a sharp increase of tumor necrosis factor and leukemia inhibitory factor production and was controlled by the mouse genetic background. The viral infection led to an imbalance in the cytokine response to LPS, with an enhancement of pro-inflammatory cytokines, including IL-18 and IFN-γ and a delayed secretion of anti-inflammatory IL-10 that could result in exacerbated macrophage activation. Enhanced IFN-γ production was involved in the virus-induced susceptibility to shock. In sharp contrast with other viral infections, IFN-α/β diminished IFN-γ production and the resulting increased response to LPS in LDV-infected animals. © The Japanese Society for Immunology. 2007. All rights reserved.