Apocynin inhibits reactive oxygen species (ROS) and downregulates chemokine and cytokine production induced by avian influenza H5N1and H7N9 virus infection. (INC8P.433)

Abstract

Abstract Influenza A virus infection causes acute inflammation resulting in increased reactive oxygen species (ROS) production and lung injury. ROS are produced following activation of the NADPH oxidase enzyme complex. Apocynin, an inhibitor of NADPH oxidase complex formation has been shown to reduce the accumulation of inflammatory cells in the lungs of influenza-infected mice. As hypercytokinemia is thought to contribute to severe disease pathogenesis of both H5N1 and H7N9 infection in humans, we hypothesized that apocynin could reduce virus-induced cytokine/chemokine production. Human lung epithelial and chicken cell lines were infected with low pathogenic avian influenza H7N9 (A/Anhui/1/2013) and HPAI H5N1 (A/chicken/Vietnam/0008/2004) viruses in the absence or presence of apocynin. Quantitative real-time PCR demonstrated that apocynin inhibited influenza-induced cytokines/chemokines and ROS production following infection. Interestingly, addition of apocynin to in vitro cultures significantly increased SOCS1 and SOCS3 mRNA and protein expression, contributing to the negative regulation of overall cytokine expression. We suggest that intervention strategies targeting both the virus (current therapeutics) and the host e.g. apocynin (future therapeutics) could be used to ameliorate disease in infected individuals, reducing hypercytokinemia and pathology and allowing full development of adaptive immune responses.