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Robert G. Sawyer, MD; Reid B. Adams, MD; Addison K. May, MD; Lynn K. Rosenlof, MD; Timothy L. Pruett, MD

Arch Surg. 1993;128(1):73-78.

Abstract
• The systemic tumor necrosis factor (TNF) response has been extensively studied during infection. In addition, antibiotics that cause cell-wall lysis have been associated with endotoxinemia and, therefore, could trigger TNF release. We studied the effects of pretreatment with cefoxitin and/or anti-TNF antibody on mortality and early (90 minutes) and delayed (6 hours) serum TNF levels in a murine model of mixed Escherichia coli/Bacteroides fragilis peritonitis. At low and intermediate inocula levels, cefoxitin, but not anti-TNF antibody, prevented death, and low serum TNF levels were noted in all groups. At the highest inoculum level, mortality was uniform in control, cefoxitin, and anti-TNF antibody groups, and a significant elevation in serum TNF levels was seen only at the 6-hour point in animals receiving cefoxitin. The addition of anti-TNF antibody to cefoxitin at this inoculum level abrogated the 6-hour rise in serum TNF levels and reduced mortality to 40%. These results emphasize that the cytokine response in disease is dependent on both the nature of the insult and other forms of therapeutic interventions.

(Arch Surg. 1993;128:73-78)

Author Affiliations
From the Department of Surgery, Surgical Infectious Disease Laboratory, University of Virginia, Charlottesville.

Footnotes
Accepted for publication August 15, 1992.

Presented at the 12th Annual Meeting of the Surgical Infection Society, Los Angeles, Calif, April 11, 1992, and the Fifth Annual Meeting of the Surgical Infection Society-Europe, Santiago de Compostela, Spain, June 9, 1992.

Reprint requests to Box 526, University of Virginia Hospital, Charlottesville, VA 22908 (Dr Sawyer).

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