Revhaug A, Michie H R, Manson J M, Watters J M, Dinarello C A, Wolff S M, Wilmore D W
Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115.
Arch Surg. 1988 Feb;123(2):162-70. doi: 10.1001/archsurg.1988.01400260042004.
Acute infection initiates fever, acute-phase changes, and catabolic responses in the host, resulting in weight loss, hypermetabolism, and accelerated proteolysis. To test the hypothesis that cyclo-oxygenase inhibition might attenuate these responses, we administered Escherichia coli endotoxin intravenously to seven normal volunteers and to seven additional subjects pretreated with a cyclo-oxygenase inhibitor (ibuprofen). Control studies were also performed following administration of saline and ibuprofen alone. Vital signs, metabolic rate, and concentrations of pituitary and stress hormones, as well as those of other substrates, were serially measured. Endotoxin administration produced a response similar to an acute illness, with flulike symptoms, fever, tachycardia, increased metabolic rate, and stimulation of stress hormone release. These changes were markedly attenuated by cyclo-oxygenase inhibition. The leukocytosis, hypoferremia, and elevation of the C-reactive protein level induced by endotoxin were unaffected by cyclo-oxygenase inhibition. These data indicate that activation of the cyclooxygenase pathway is necessary to produce many of the metabolic changes observed during critical illness.
急性感染会引发宿主的发热、急性期变化及分解代谢反应，导致体重减轻、代谢亢进和蛋白水解加速。为验证环氧化酶抑制可能会减弱这些反应这一假说，我们对7名正常志愿者以及另外7名预先服用环氧化酶抑制剂（布洛芬）的受试者静脉注射大肠杆菌内毒素。还分别进行了单独注射生理盐水和布洛芬后的对照研究。连续测量生命体征、代谢率、垂体和应激激素浓度以及其他底物的浓度。注射内毒素后产生了类似于急性疾病的反应，出现流感样症状、发热、心动过速、代谢率增加以及应激激素释放受到刺激。这些变化因环氧化酶抑制而明显减弱。内毒素诱导的白细胞增多、低铁血症和C反应蛋白水平升高不受环氧化酶抑制的影响。这些数据表明，环氧化酶途径的激活对于产生危重病期间观察到的许多代谢变化是必要的。
