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Chan, M. C. et al. Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells. Respir. Res. 6, 135

Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region of China.
Respiratory research (Impact Factor: 3.09). 02/2005; 6(1):135. DOI: 10.1186/1465-9921-6-135
Source: PubMed

ABSTRACT

Fatal human respiratory disease associated with influenza A subtype H5N1 has been documented in Hong Kong, and more recently in Vietnam, Thailand and Cambodia. We previously demonstrated that patients with H5N1 disease had unusually high serum levels of IP-10 (interferon-gamma-inducible protein-10). Furthermore, when compared with human influenza virus subtype H1N1, the H5N1 viruses in 1997 (A/Hong Kong/483/97) (H5N1/97) were more potent inducers of pro-inflammatory cytokines (e.g. tumor necrosis factor-a) and chemokines (e.g. IP-10) from primary human macrophages in vitro, which suggests that cytokines dysregulation may play a role in pathogenesis of H5N1 disease. Since respiratory epithelial cells are the primary target cell for replication of influenza viruses, it is pertinent to investigate the cytokine induction profile of H5N1 viruses in these cells.
We used quantitative RT-PCR and ELISA to compare the profile of cytokine and chemokine gene expression induced by H5N1 viruses A/HK/483/97 (H5N1/97), A/Vietnam/1194/04 and A/Vietnam/3046/04 (both H5N1/04) with that of human H1N1 virus in human primary alveolar and bronchial epithelial cells in vitro.
We demonstrated that in comparison to human H1N1 viruses, H5N1/97 and H5N1/04 viruses were more potent inducers of IP-10, interferon beta, RANTES (regulated on activation, normal T cell expressed and secreted) and interleukin 6 (IL-6) in primary human alveolar and bronchial epithelial cells in vitro. Recent H5N1 viruses from Vietnam (H5N1/04) appeared to be even more potent at inducing IP-10 than H5N1/97 virus.
The H5N1/97 and H5N1/04 subtype influenza A viruses are more potent inducers of proinflammatory cytokines and chemokines in primary human respiratory epithelial cells than subtype H1N1 virus. We suggest that this hyper-induction of cytokines may be relevant to the pathogenesis of human H5N1 disease.

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    • "During highly pathogenic H5N1 infection, cytokine storm was hypothesized to be a cause of tissue damage, ultimately contributing to death. Especially, increased levels of proinflammatory cytokines including TNF-a and IL-6, have been observed in human and mice infected with highly pathogenic H5N1 influenza virus (Chan et al., 2005; Cheung et al., 2002; de Jong et al., 2005; Lee et al., 2005; Szretter et al., 2007; Xu et al., 2006 "
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    • "Interestingly, a clinical study found elevated IP-10 levels to be a potential biomarker for severe acute respiratory virus infections [36]. Human airway epithelial cells have already been shown to release IP-10 in response to influenza A H5N1 infection [37]. This is in congruence with the results of this study since HAdV-B14p1 infection of differentiated bronchial epithelial cells resulted in a significant IP-10 and additionally I-Tac induction and release. "
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