Anti-tumor necrosis factor antibody reduces mortality in the presence of antibiotic-induced tumor necrosis factor release
R. G. Sawyer, R. B. Adams, A. K. May, L. K. Rosenlof and T. L. Pruett
Department of Surgery, University of Virginia, Charlottesville.
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.