Divergent roles of IFNs in the sensitization to endotoxin shock by lactate dehydrogenase-elevating virus.
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-gamma and a delayed secretion of anti-inflammatory IL-10 that could result in exacerbated macrophage activation. Enhanced IFN-gamma production was involved in the virus-induced susceptibility to shock. In sharp contrast with other viral infections, IFN-alpha/beta diminished IFN-gamma production and the resulting increased response to LPS in LDV-infected animals.
Le-Thi-Phuong
Thao
T
Unit of Experimental Medicine, Université Catholique de Louvain, UCL MEXP 7430, 1200 Bruxelles, Belgium.
Dumoutier
Laure
L
Renauld
Jean-Christophe
JC
Van Snick
Jacques
J
Coutelier
Jean-Paul
JP
D000818:Animals; D018174:Arterivirus Infections / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000276:immunology; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D007372:Interferons / Q000276:immunology*; D007772:Lactate dehydrogenase-elevating virus / Q000276:immunology* / Q000472:pathogenicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D012772:Shock, Septic / Q000276:immunology*
D016207:Cytokines; D004731:Endotoxins; D007372:Interferons