Anti-tumor necrosis factor antibody reduces mortality in the presence of antibiotic-induced tumor necrosis factor release.
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.
Sawyer
R G
RG
Department of Surgery, University of Virginia, Charlottesville.
Adams
R B
RB
May
A K
AK
Rosenlof
L K
LK
Pruett
T L
TL
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001442:Bacteroides Infections / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D001441:Bacteroides fragilis; D002440:Cefoxitin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D004927:Escherichia coli Infections / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D007074:Immunoglobulin G; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010538:Peritonitis / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D002440:Cefoxitin