The effects of tumor necrosis factor and their selective inhibition by ibuprofen

D. A. Evans, D. O. Jacobs, A. Revhaug, D. W. Wilmore

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

High doses of tumor necrosis factor (TNF) cause hypotension, metabolic acidosis and, death. At Brigham and Women's Hospital, the effects of a sublethal, 6-hour infusion of TNF (0.57 x 105 Units/kg body weight) in twelve anesthetized dogs were studied. This dose caused falls in mean arterial pressure from 153 mmHg to 96 mmHg, pulmonary artery pressure (-4.5 mmHg), central venous pressure (-2.5 mmHg) and pulmonary capillary wedge pressures (-5.25 mmHg). Associated with these responses were a fourfold increase in urine volume (22.4 ml/kg/6 hours as compared to 5.2 ml/kg/6 hours in controls), significant pyrexia (from 38.1 C to 39.5 C, rectal), tachycardia (from 125 to 175 beats/minute), and hypermetabolism. In addition, leukopenia and increased circulating stress hormone concentrations were observed. Blood glucose concentrations fell from 4.68 mM/l to 3.97 mM/l (84-71 mg/dl) within 3 hours of TNF infusion, whereas lactate and pyruvate concentrations increased. These alterations occurred in the absence of severe hypotension or acidosis and were similar to changes observed after endotoxin administration or gram-negative septicemia. Pretreatment of the animals with the cyclooxygenase inhibitor ibuprofen abolished most of the hemodynamic changes and attenuated other responses. These findings support the hypothesis that TNF is an important mediator of septic responses and that some of the effects of TNF are mediated via cyclooxygenase pathways.

Original languageEnglish (US)
Pages (from-to)312-321
Number of pages10
JournalAnnals of Surgery
Volume209
Issue number3
StatePublished - 1989
Externally publishedYes

Fingerprint

Ibuprofen
Tumor Necrosis Factor-alpha
Acidosis
Hypotension
Central Venous Pressure
Pulmonary Wedge Pressure
Cyclooxygenase Inhibitors
Leukopenia
Prostaglandin-Endoperoxide Synthases
Pyruvic Acid
Tachycardia
Endotoxins
Pulmonary Artery
Blood Glucose
Lactic Acid
Sepsis
Arterial Pressure
Fever
Hemodynamics
Body Weight

ASJC Scopus subject areas

  • Surgery

Cite this

Evans, D. A., Jacobs, D. O., Revhaug, A., & Wilmore, D. W. (1989). The effects of tumor necrosis factor and their selective inhibition by ibuprofen. Annals of Surgery, 209(3), 312-321.

The effects of tumor necrosis factor and their selective inhibition by ibuprofen. / Evans, D. A.; Jacobs, D. O.; Revhaug, A.; Wilmore, D. W.

In: Annals of Surgery, Vol. 209, No. 3, 1989, p. 312-321.

Research output: Contribution to journalArticle

Evans, DA, Jacobs, DO, Revhaug, A & Wilmore, DW 1989, 'The effects of tumor necrosis factor and their selective inhibition by ibuprofen', Annals of Surgery, vol. 209, no. 3, pp. 312-321.
Evans DA, Jacobs DO, Revhaug A, Wilmore DW. The effects of tumor necrosis factor and their selective inhibition by ibuprofen. Annals of Surgery. 1989;209(3):312-321.
Evans, D. A. ; Jacobs, D. O. ; Revhaug, A. ; Wilmore, D. W. / The effects of tumor necrosis factor and their selective inhibition by ibuprofen. In: Annals of Surgery. 1989 ; Vol. 209, No. 3. pp. 312-321.
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