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Arthur Revhaug, MD; Hamish R. Michie, FRCS(E); James McK. Manson, FRCS(E); James M. Watters, MD; Charles A. Dinarello, MD; Sheldon M. Wolff, MD; Douglas W. Wilmore, MD

Arch Surg. 1988;123(2):162-170.

Abstract
• 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.

(Arch Surg 1988;123:162-170)

Author Affiliations
From the Laboratories for Surgical Metabolism and Nutrition, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston (Drs Revhaug, Michie, Manson, Watters, and Wilmore); and Department of Medicine, New England Medical Center and Tufts University School of Medicine, Boston (Drs Dinarello and Wolff). Dr Revhaug was the Johnson & Johnson Scholar recipient of the Surgical Infection Society, 1986-1987.

Footnotes
Accepted for publication Aug 3, 1987.

Read before the Seventh Annual Meeting of the Surgical Infection Society, Philadelphia, May 12, 1987.

Reprint requests to Department of Surgery, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115 (Dr Wilmore).

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