Pharmacologic Inhibition of COX-1 and COX-2 in Influenza A Viral Infection in Mice

被引:57
|
作者
Carey, Michelle A. [1 ]
Bradbury, J. Alyce [1 ]
Rebolloso, Yvette D. [1 ]
Graves, Joan P. [1 ]
Zeldin, Darryl C. [1 ]
Germolec, Dori R. [1 ]
机构
[1] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA
来源
PLOS ONE | 2010年 / 5卷 / 07期
基金
美国国家卫生研究院;
关键词
COLONY-STIMULATING FACTOR; G-CSF; ALLERGIC INFLAMMATION; IMMUNE-RESPONSE; DEFICIENT MICE; VIRUS; HYPOTHERMIA; CYCLOOXYGENASES; PROSTAGLANDINS; GRANULOCYTE;
D O I
10.1371/journal.pone.0011610
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: We previously demonstrated that cyclooxygenase (COX)-1 deficiency results in greater morbidity and inflammation, whereas COX-2 deficiency leads to reduced morbidity, inflammation and mortality in influenza infected mice. Methodology/Principal Findings: We investigated the effects of COX-1 and COX-2 inhibitors in influenza A viral infection. Mice were given a COX-1 inhibitor (SC-560), a COX-2 inhibitor (celecoxib) or no inhibitor beginning 2 weeks prior to influenza A viral infection (200 PFU) and throughout the course of the experiment. Body weight and temperature were measured daily as indicators of morbidity. Animals were sacrificed on days 1 and 4 post-infection and bronchoalveolar lavage (BAL) fluid was collected or daily mortality was recorded up to 2 weeks post-infection. Treatment with SC-560 significantly increased mortality and was associated with profound hypothermia and greater weight loss compared to celecoxib or control groups. On day 4 of infection, BAL fluid cells were modestly elevated in celecoxib treated mice compared to SC-560 or control groups. Viral titres were similar between treatment groups. Levels of TNF-alpha and G-CSF were significantly attenuated in the SC-560 and celecoxib groups versus control and IL-6 levels were significantly lower in BAL fluid of celecoxib treated mice versus control and versus the SC-560 group. The chemokine KC was significantly lower in SC-560 group versus control. Conclusions/Significance: Treatment with a COX-1 inhibitor during influenza A viral infection is detrimental to the host whereas inhibition of COX-2 does not significantly modulate disease severity. COX-1 plays a critical role in controlling the thermoregulatory response to influenza A viral infection in mice.
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页数:8
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