Editorial [Hot Topic:Avian and Pandemic Influenza Cytokine Storm, Inflammation,Tissue and Therapeutic Opportunities (Guest Editor: Jonathan P. Wong)]

Despite advances in vaccine development and antiviral drug chemotherapy, the world is still ill equipped to defend against future influenza pandemics. The vulnerability of humans to pandemic influenza was particularly evident during the 1918-19 Spanish flu pandemic which killed 20-50 millions people globally. The current global bird flu crisis in Asia, Africa and Europe has sparked fear of another influenza pandemic and again expose our vulnerability. The goals of this special issue entitled “Avian and pandemic influenza: cytokine storm, inflammation, tissue injuries and therapeutic opportunities” are two-fold. Firstly, to provide a comprehensive review on the pathogenicity of deadly influenza viruses and on the mechanisms virus-induced induce massive inflammation and apoptosis in the respiratory tract. Secondly, to present a forum to highlight therapeutic approaches that could be used to mitigate the devastating effects of inflammatory and apoptosis, and how they may have a role to play in improving clinical outcome in humans. This special issue is comprised of original and review articles contributed by some of the leading experts in immunology, virology, molecular biology and clinical medicine. The first 2 articles by Morris et al., and Wareing and Tannock, outlined the immunological mechanisms of “cytokine storm” characterized by apoptosis and overinduction of various pro-inflammatory cytokines, which is closely linked to activation of caspase pathway and clinical disease severity. This activation of the proinflammatory cytokines and apoptosis lead to pulmonary edema and destruction of the respiratory epithelium in various animal models were documented using a reconstructed 1918-19 Spanish influenza virus (Suresh and Kobasa). Cellular immune responses to influenza virus infections, particularly memory T-cells (Halwani et al.) and phagocytes (Nakanishi et al.), and their roles in the pathogenicity of and constituting to protective antiviral immunity to influenza infections are addressed. The second part of this issue focuses on therapeutic opportunities to counter the deadly effects on influenza viral inducedinflammation and apoptosis. Recent clinical findings have shown that treatment of inflammation in avian influenza patients with corticosteroid had resulted in higher fatality rate compared to those who did not receive corticosteroids (New Engl. J. Med. 358:261-273, 2008). It is therefore important to explore novel therapeutic agents other than corticosteroids to counter this inflammatory effect and to improve survival in these patients. Dale et al., presented promising results that provide evidence that short nano RNA oligonucleotides directed against non-structural viral protein are effective in the reducing the inflammatory effects and enhancing the antiviral efficacy against the highly pathogenic avian H5N1 influenza virus infection. V. Khudoley et al. presented a review comprising a number of studies that suggest Jodantipyrin, an old anti-inflammatory drug that induces interferon, has broad-spectrum antiviral effect and has been shown in clinical efficacy against influenza virus infections. The articles by Cairns et al., and Hu et al., described novel approaches using small interfering RNAs (siRNA) and humanized antibody fragments to either silence the expression of viral proteins and/or reduce virus-induced inflammation, respectively. The potential applications of these approaches and their efficacies will need to be determined against the deadly influenza viruses. Davids et al., described an important study to explore the beneficial effects of anti-inflammatory proteins produced by viruses and how they can be used for the treatment of cancers and prevention of angiogenesis and metastasis.