Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.
PLoS One. 2010 Jul 15;5(7):e11610. doi: 10.1371/journal.pone.0011610.
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.
我们之前的研究表明，环氧化酶（COX）-1 缺乏会导致更高的发病率和炎症，而 COX-2 缺乏则会导致流感感染小鼠的发病率、炎症和死亡率降低。
方法/主要发现：我们研究了 COX-1 和 COX-2 抑制剂在甲型流感病毒感染中的作用。小鼠在感染流感病毒（200PFU）前 2 周开始给予 COX-1 抑制剂（SC-560）、COX-2 抑制剂（塞来昔布）或不给予抑制剂，并在整个实验过程中给予抑制剂。每日测量体重和体温作为发病率的指标。感染后第 1 天和第 4 天处死动物，并收集支气管肺泡灌洗液（BAL）或记录每日死亡率，直至感染后 2 周。与塞来昔布或对照组相比，SC-560 治疗显著增加了死亡率，并伴有严重的体温过低和体重减轻。感染后第 4 天，与 SC-560 或对照组相比，塞来昔布治疗组的 BAL 液细胞略有升高。治疗组之间的病毒滴度相似。与对照组相比，SC-560 和塞来昔布组的 TNF-α 和 G-CSF 水平显著降低，IL-6 水平在塞来昔布治疗组的 BAL 液中明显低于对照组和 SC-560 组。趋化因子 KC 在 SC-560 组明显低于对照组。
结论/意义：流感 A 病毒感染期间使用 COX-1 抑制剂对宿主有害，而 COX-2 抑制不会显著调节疾病严重程度。COX-1 在控制流感 A 病毒感染小鼠的体温调节反应中起着关键作用。
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