Cytokine profiles induced by the novel swine-origin influenza A/H1N1 virus: implications for treatment strategies.
BACKGROUND. Given the apparent high mortality associated with the novel swine-origin influenza A/H1N1 virus (S-OIV) in Mexico, we aimed to study the cytokine profiles induced by S-OIV and the effect of immunomodulators. METHODS. We assayed cytokines and their messenger RNA (mRNA) levels in culture supernatants of human macrophages infected with H5N1, S-OIV California/04/2009 (S-OIV-CA), S-OIV Hong Kong/415742 (S-OIV-HK), or seasonal H1N1 with or without celecoxib and mesalazine. RESULTS. Among the 12 cytokines showing detectable levels, levels of 8 proinflammatory cytokines (interleukin [IL] 2R, IL-6, interferon [IFN] alpha, macrophage inflammatory protein [MIP] alpha, MIP-1beta, IFN-induced protein 10, regulated on activation, normal T cell expressed and secreted [RANTES], and monocyte chemotactic protein [MCP] 1) were higher in cells infected by H5N1 but similar among cells infected with H1N1, S-OIV-CA, or S-OIV-HK. The levels of the other 4 cytokines were similar for H5N1, H1N1, S-OIV-CA and S-OIV-HK. Among the 8 cytokines induced by H5N1, 6 were suppressed by celecoxib and mesalazine. The mRNA levels of tumor necrosis factor alpha, IFN-gamma, IL-6, and MCP-1 induced by H5N1 were higher than the levels of other cytokines at 12 and/or 24 h. CONCLUSIONS. No major cytokine storm, as seen in H5N1 infection, is associated with S-OIV infection of cell lines. The mainstay of treatment for uncomplicated S-OIV infections should be antiviral agents without immunomodulators. For individual S-OIV-infected patients with severe primary viral pneumonia, severe sepsis, and multiorgan failure, immunomodulators may be considered as an adjunctive therapy in clinical trials.
Woo
Patrick C Y
PC
State Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong, China.
Tung
Edward T K
ET
Chan
Kwok-Hung
KH
Lau
Candy C Y
CC
Lau
Susanna K P
SK
Yuen
Kwok-Yung
KY
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology / Q000472:pathogenicity; D008264:Macrophages / Q000378:metabolism* / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013552:Swine
D016207:Cytokines; D012333:RNA, Messenger