Contrasting Effects of Cyclooxygenase-1 (COX-1) and COX-2 Deficiency on the Host Response to Influenza A Viral Infection

• Published in: Journal of Immunology 2005-11, Vol.175 (10), p.6878-6884
• Main Authors: Carey, Michelle A, Bradbury, J. Alyce, Seubert, John M, Langenbach, Robert, Zeldin, Darryl C, Germolec, Dori R
• Format: Article
• Language: English
• Subjects: Animals; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - immunology; Cyclooxygenase 1 - deficiency; Cyclooxygenase 1 - genetics; Cyclooxygenase 2 - deficiency; Cyclooxygenase 2 - genetics; Cytokines - biosynthesis; Dinoprostone - metabolism; Disease Models, Animal; Female; Humans; Inflammation Mediators - metabolism; Influenza A Virus, H3N2 Subtype - isolation & purification; Influenza, Human - enzymology; Influenza, Human - immunology; Influenza, Human - virology; Lung - virology; Mice; Mice, Inbred C57BL; Mice, Knockout
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.175.10.6878

Influenza is a significant cause of morbidity and mortality worldwide despite extensive research and vaccine availability. The cyclooxygenase (COX) pathway is important in modulating immune responses and is also a major target of nonsteroidal anti-inflammatory drugs (NSAIDs) and the newer COX-2 inhibitors. The purpose of the present study was to examine the effect of deficiency of COX-1 or COX-2 on the host response to influenza. We used an influenza A viral infection model in wild type (WT), COX-1-/-, and COX-2-/- mice. Infection induced less severe illness in COX-2-/- mice in comparison to WT and COX-1-/- mice as evidenced by body weight and body temperature changes. Mortality was significantly reduced in COX-2-/- mice. COX-1-/- mice had enhanced inflammation and earlier appearance of proinflammatory cytokines in the BAL fluid, whereas the inflammatory and cytokine responses were blunted in COX-2-/- mice. However, lung viral titers were markedly elevated in COX-2-/- mice relative to WT and COX-1-/- mice on day 4 of infection. Levels of PGE2 were reduced in COX-1-/- airways whereas cysteinyl leukotrienes were elevated in COX-2-/- airways following infection. Thus, deficiency of COX-1 and COX-2 leads to contrasting effects in the host response to influenza infection, and these differences are associated with altered production of prostaglandins and leukotrienes following infection. COX-1 deficiency is detrimental whereas COX-2 deficiency is beneficial to the host during influenza viral infection.