High susceptibility to lipopolysaccharide-induced lethal shock in encephalomyocarditis virus-infected mice (original) (raw)

Secondary bacterial infection in humans is one of the pathological conditions requiring clinical attention. In this study, we examined the effect of lipopolysaccharide (LPS) on encephalomyocarditis virus (EMCV) infected mice. All mice inoculated with EMCV at 5 days before LPS challenge died within 24 h. LPS-induced TNF-a mRNA expression was significantly increased in the brain and heart at 5 days after EMCV infection. CD11b 1 /TLR4 1 cell population in the heart was remarkably elevated at 5 days after EMCV infection, and sorted CD11b 1 cells at 5 days after EMCV infection produced a large amount of TNF-a on LPS stimulation in vivo and in vitro. In conclusion, we found that the infiltration of CD11b 1 cells into infected organs is involved in the subsequent LPS-induced lethal shock in viral encephalomyocarditis. This new experimental model can help define the mechanism by which secondary bacterial infection causes a lethal shock in viral encephalomyocarditis. P olymicrobial infectious diseases show the involvement of 2 or more microbes, including viruses, bacteria, fungi or parasites, and these microbes act synergistically to mediate complex disease processes. In particular, a bacterial infection superimposed over an acute viral infection such as influenza is well known as the aggravation factor in the infectious disease 1,2 . Lipopolysaccharide (LPS), the outer membrane of gram-negative bacteria, causes systemic inflammatory response syndrome, endotoxic shock, disseminated intravascular coagulation and multi-organ failure 3,4 . LPS is recognized by Toll-like receptor 4 (TLR4)-expressing immunocompetent cells, mainly monocytes and macrophages, and induces the production of inflammatory cytokines through NF-kB activation 3 . Toxic effects of LPS are partially induced by the release and action of macrophage-derived inflammatory cytokines. Especially, the mass production of tumor necrosis factor-a (TNF-a) causes septic shock with an abrupt reduction in blood pressure, leading to rapid aggravation of the disease condition 5,6 . It is known that LPS-induced lethal shock is caused by a large quantity of TNF-a produced by immune cells activated by some kind of pre-stimulation 7,8 .