Expression Profiles Of Cytokines In Lung Of Mice Infected With H4N2 Subtype Avian Influenza Virus

H4N2 subtype avian influenza virus poses a potential threat to the health of human and mammalian.The mouse-adapted virus P20 and P50 of A/duck/shanghai/29-1/2009(H4N2)showed significantly different morbidity and mortality in mice.To investigate the roles of inflammation-associated cytokines in development of disease,mice were inoculated intranasally with 106EID50of P20 and P50 viruses.At 1,3 and 5 days post infection,the expression of anti-inflammatory cytokines(IL-2,IL-4 and IL-10),pro-inflammation cytokines(IL-1?,IL-6 and TNF-?),monocyte chemoattractant protein-1(MCP-1)and interferon ?/?/?(IFN-?/?/?)in lungs were detected respectively by ELISA and real-time PCR.The results showed that the expression of IL-1?,IL-6,IL-10,MCP-1,IFN-? and TNF-? were up-regulated,while IL-2,IL-4 and IFN-?/? were down-regulated after the infection of both viruses.Compared with P20infected mice,the expression levels of IL-1?,IL-10,MCP-1,IFN-? and IL-6 in lungs of P50infected mice were significantly increased at different days.In particular,the mRNA level of IL-6increased significantly at 3 and 5 days post infection.To validate the role of IL-6 in pro-inflammation,mice were inoculated intravenously with anti-IL-6 neutralizing antibody after inoculated intranasally with P50 virus.The results showed that IL-6 expression level was decreased clearly in the lungs but the inflammatory reaction and pathogenicity had not been alleviated in mice.The study suggested that the pathogenicity of H4N2 subtype avian influenza virus in mice was associated with inflammatory response,but decreased IL-6 expression did not alleviate the inflammatory reaction.