Intensive cytokine induction in pandemic H1N1 influenza virus infection accompanied by robust production of IL-10 and IL-6

• Published in: PloS one 2011-12, Vol.6 (12), p.e28680-e28680
• Main Authors: Yu, Xuelian, Zhang, Xi, Zhao, Baihui, Wang, Jiayu, Zhu, Zhaokui, Teng, Zheng, Shao, Junjie, Shen, Jiaren, Gao, Ye, Yuan, Zhengan, Wu, Fan
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Adults; Age; Antibodies, Viral - immunology; Biology; Body Temperature; Case-Control Studies; Chemokines; Child; Child, Preschool; China - epidemiology; Correlation analysis; Cytokines; Development and progression; Disease control; Disease prevention; Enzyme-linked immunosorbent assay; Epidemics; Fatalities; Female; Gene expression; Health aspects; Humans; Identification methods; Immune response; Immune system; Infant; Infections; Influenza; Influenza A Virus, H1N1 Subtype - immunology; Influenza viruses; Influenza, Human - blood; Influenza, Human - epidemiology; Influenza, Human - immunology; Influenza, Human - virology; Innate immunity; Interferon; Interleukin 1; Interleukin 10; Interleukin 12; Interleukin 17; Interleukin 2; Interleukin 23; Interleukin 4; Interleukin 5; Interleukin 6; Interleukin 8; Interleukin-10 - biosynthesis; Interleukin-10 - blood; Interleukin-6 - biosynthesis; Interleukin-6 - blood; Lymphocytes T; Male; Medical laboratories; Medical research; Medicine; Melanoma; Metastasis; Pandemics; Pandemics - statistics & numerical data; Pathogenesis; Patients; Severity of Illness Index; Studies; Swine flu; Swine influenza; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Vaccination; Viral infections; Virus diseases; Viruses; Young adults; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0028680

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. 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. 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.