Role of Apoptosis and Proinflammatory Cytokines in Influenza Virus Morbidity and Mortality

Author(s): Susan Jane Morris, Edward William Andrew Brydon, Clive Sweet

Journal Name: Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Formerly Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents

Volume 7 , Issue 2 , 2008

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Influenza virus is a major human pathogen that causes epidemics and pandemics with increased morbidity and, especially in the elderly and those with pre-existing medical conditions, increased mortality. Currently avian influenza viruses are causing deaths in previously “not-at-risk” groups. Influenza is characterised by respiratory symptoms and constitutional symptoms. In this review we explore current knowledge of the role inflammation and apoptosis plays in respiratory epithelial cell damage and pathogenicity. Influenza virus vRNA, other ssRNAs and dsRNAs are recognised by cellular pathogen-associated microbial pattern (PAMP) receptors. Of these, TLR3 activates NF-κB, a transcription factor of pro-inflammatory cytokines such as TNF-α, IL-1 and IL-6 along with a variety of chemokines like CCL2, CCL3, CCL4, CCL5, CXCL8 and CXCL10, and Type 1 interferons (IFN) through the IFN regulator IRF3. TLR7/TLR8 activates NF-κB through different mediators to stimulate a similar response. Pro-inflammatory and antiviral cytokines may also be induced by TLR3/TLR7-independent pathways involving NOD-like receptors and CARD-helicase proteins. It is also becoming clearer that the mechanisms leading to inflammatory responses and to apoptosis are linked particularly with regard to caspase activation and function. The role these pathways play in influenza virus induced mortality and morbidity will be discussed with particular reference to that of the H5N1 viruses.

Keywords: Influenza virus, apoptosis, fever, constitutional symptoms, respiratory symptoms, cytokines, chemokines

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Article Details

Year: 2008
Page: [59 - 70]
Pages: 12
DOI: 10.2174/187152308784533168
Price: $65

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PDF: 6