Regulation of Proinflammatory Cytokine by Vitmain B2 in Influenza A/H5N1 Virus Infected Human Alveolar Epithelial Cells and Macrophages

Abstract

Highly pathogenic avian influenza (HPAI) H5N1 virus is entrenched in poutlry and continues to transmit zoonotically to humans posing a pandemic threat. In preparation for next pandemic, governments all over the world have stockpiled oseltamivir and other antivirals. However, in case of a pandemic, time will be required before a safe and reliable vaccine becomes available. Thus there is a urgent need for adjunctive therapies that may help modulate the severity of the disease. Human H5N1 disease causes unusual disease severity and high mortality, and clinical syndromes have been previously suggested to associate with cytokine dysregulation. Vitamin B2 was shown previously to lowers the serum levels of cytokines and chemokines and improves survival rate in bacterial sepsis models in rodents. This result suggests vitamin B2, could be a promising alternative strategy for the treatment of severe human influenza diseases by modulating the adverse innate immune responses. In this study, we infected the primary human alveolar epithelial cells and peripheral blood derived macrophage with influenza A viruses (H5N1 and H1N1) with or without vitamin B2 treatment and to detemine the mRNA and protein expression of proinflammatory cytokine and chemokine by real-time quantitative RT-PCR and ELISA respectively. Our studies have shown that vitamin B2 is effective in suppressing the hyper induction of cytokine and chemokine (TNF-alpha, IP10, RANTES) upon influenza H5N1 virus infection in alveolar epithelial cells and macrophages in vitro. We hypothese vitamin B2 can be a potential candidate to alleviate the pathology of human H5N1 disease by modulating the host innate immune responses. Understanding the host interaction with influenza virus and the role of vitamin B2 as immunomodulatory agents in human H5N1 disease can provide important insight into the mechanism of pathogenesis and to identify allternative therapy for treatment of avian influenza H5N1 disease.