C-Reactive Protein Mediating Immunopathological Lesions: A Potential Treatment Option for Severe Influenza A Diseases
Rongbao Gao,
Lijie Wang,
Tian Bai,
Ye Zhang,
Hong Bo,
Yuelong Shu
Affiliations
Rongbao Gao
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing 102206, China
Lijie Wang
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing 102206, China
Tian Bai
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing 102206, China
Ye Zhang
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing 102206, China
Hong Bo
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing 102206, China
Yuelong Shu
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing 102206, China
Severe influenza diseases with high mortality have been frequently reported, especially in those patients infected with avian influenza A (H5N1, H7N9 or H10N8) or during a pandemic. Respiratory distress, which is attributed to alveolar damage associated with immunopathological lesions, is the most common cause of death. There is a wealth of information on pathogenesis or treatment options. In this study, we showed that high levels of C-reactive protein (CRP) were induced and correlated with complement activation in patients infected with severe influenza A (H5N1, H7N9 or H10N8), and higher levels were induced in fatal patients than in survivors. CRP treatment enhanced the phagocytosis of monocytes THP-1 to H5N1 virus as well as the expression of proinflammatory cytokines or apoptosis-associated genes in THP-1 cells or pneumocytes A-549 respectively. CRP may link to proinflammatory mediators contributing to activation of complement and boosting inflammatory response in severe influenza infections. Compound 1,6-bis(phosphocholine)-hexane improved the severity and mortality of mice infected with lethal influenza virus significantly. These observations showed that CRP is involved in deterioration of severe influenza diseases, and indicated a substantial candidate molecule for immunotherapy of severe influenza diseases.
