Contrasting effects of cyclooxygenase-1 (COX-1) and COX-2 deficiency on the host response to influenza A viral infection

被引:93
作者
Carey, MA
Bradbury, JA
Seubert, JM
Langenbach, R
Zeldin, DC
Germolec, DR
机构
[1] NIH, NIEHS, Div Intramural Res, Lab Resp Biol, Res Triangle Pk, NC 27709 USA
[2] NIH, NIEHS, Div Intramural Res, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA
[3] NIH, NIEHS, Div Intramural Res, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA
关键词
D O I
10.4049/jimmunol.175.10.6878
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 antiinflammatory 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 PGE(2) 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.
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页码:6878 / 6884
页数:7
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