05 were taken to indicate statistical significance. Results Administration of the TNF inhibitor etanercept significantly improved survival of H1N1 infected mice and reduced pulmonary injury Mice were treated selleck chemicals with either saline or etanercept i. n. after intranasal infection with the lethal mouse adapted human influenza virus A FM 1 47. Etanercept administration significantly increased the survival of mice, compared with the control mice. For recipi ents of saline alone, no mice survived beyond 7 days after infection, whereas 30% of mice that received etanercept survived until 14 days after infection, Inhibitors,Modulators,Libraries which was the end of the observation period. In mice treated with etanercept, body weight loss ceased on day 4 after infection and slowly recovered until the end of the experiment at day 14.

Obvious indi vidual differences were also observed in etanercept treated mice after 7 days, and whether they were related to ceasing of etanercept will be clarified in future work. Lung body index demonstrated that infection with H1N1 caused lung tissue swelling Inhibitors,Modulators,Libraries and the production of significant amounts of exudate in the control mice. The administration of etanercept significantly alleviated lung swelling and exudate, Inhibitors,Modulators,Libraries an observation that was confirmed by the histopathologic analysis. Histopathologic analysis of lungs from the infected mice treated with etanercept revealed markedly reduced tissue injury, mononuclear cell accumulation, hemorrhage, and pulmonary edema. In addition, etanercept significantly reduced tissue inflammation scores compared with con trol mice on day 4 after infection.

Etanercept inhibited the burst of inflammatory cytokines and the recruitment Inhibitors,Modulators,Libraries of innate immune cells induced by lethal influenza virus infection Robust innate proinflammatory cytokine expression can cause direct tissue insult and recruit potentially tissue destructive inflammatory cells. We selected three Inhibitors,Modulators,Libraries import ant inflammatory cytokines to evaluate the cytokine burst in lethally influenza infected mice. ELISA results revealed that these cytokines increased in the virus infected control mice as expected, but they were significantly inhibited in mice treated with eta nercept. The recruitment and infiltration of immune cells can be affected by inflammatory cyto kine production.

Analysis with flow cytometry revealed a consistent reduction in the accumulation of macro phage monocytes and neutrophils in the lungs of mice treated with etanercept on 2 and 4 days after influenza A virus infection. Many significant differences were noted in neutrophils accumulation between FTY720 Multiple Sclerosis virus control and etanercept treated mice. The NK cell, an innate immune cell that plays an important role in controlling and clearing virus, count significantly decreased after infection. The administration of etanercept counteracted this reduction in NK cells.