title: Intensive cytokine induction in pandemic H1N1 influenza virus infection accompanied by robust production of IL-10 and IL-6.
abstract: BACKGROUND
  The innate immune system is the first line of defense against viruses by inducing expression of cytokines and chemokines. Many pandemic influenza H1N1 virus [P(H1N1)] infected severe cases occur in young adults under 18 years old who were rarely seriously affected by seasonal influenza. Results regarding host cytokine profiles of P(H1N1) are ambivalent. In the present study we investigated host cytokine profiles in P(H1N1) patients and identified cytokines related to disease severity.
  
  
  RESULTS
  We retrieved 77, 59, 26 and 26 sera samples from P(H1N1) and non-flu influenza like illness (non-ILIs) cases with mild symptoms (mild patients), P(H1N1) vaccinees and healthy individuals, respectively. Nine and 16 sera were from hospitalized P(H1N1) and non-ILIs patients with severe symptoms (severe patients). Cytokines of IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were assayed by cytokine bead array, IL-17 and IL-23 measured with ELISA. Mild P(H1N1) patients produced significantly elevated IL-2, IL-12, IFN-γ, IL-6, TNF-α, IL-5, IL-10, IL-17 and IL-23 versus to healthy controls. While an overwhelming IL-6 and IL-10 production were observed in severe P(H1N1) patients. Higher IL-10 secretion in P(H1N1) vaccinees confirmed our observation that highly increased level of sera IL-6 and IL-10 in P(H1N1) patients may lead to disease progression.
  
  
  CONCLUSIONS
  A comprehensive innate immune response was activated at the early stage of P(H1N1) infection with a combine Th1/Th2/Th3 cytokines production. As disease progression, a systemic production of IL-6 and IL-10 were observed in severe P(H1N1) patients. Further analysis found a strong correlation between IL-6 and IL-10 production in the severe P(H1N1) patients. IL-6 may be served as a mediator to induce IL-10 production. Highly elevated level of sera IL-6 and IL-10 in P(H1N1) patients may lead to disease progression, but the underlying mechanism awaits further detailed investigations.
authors.affiliation: Microbiology Laboratory, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, People's Republic of China.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Yu
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.forename: Baihui
authors.initials: B
authors.lastname: Zhao
authors.forename: Jiayu
authors.initials: J
authors.lastname: Wang
authors.forename: Zhaokui
authors.initials: Z
authors.lastname: Zhu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Teng
authors.forename: Junjie
authors.initials: J
authors.lastname: Shao
authors.forename: Jiaren
authors.initials: J
authors.lastname: Shen
authors.forename: Ye
authors.initials: Y
authors.lastname: Gao
authors.forename: Zhengan
authors.initials: Z
authors.lastname: Yuan
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology; D001831:Body Temperature; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D005260:Female; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000097:blood / Q000453:epidemiology* / Q000276:immunology* / Q000821:virology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D008297:Male; D058873:Pandemics / Q000706:statistics & numerical data*; D012720:Severity of Illness Index; D014611:Vaccination
chemical_list: D000914:Antibodies, Viral; D015850:Interleukin-6; D016753:Interleukin-10