Failure of prophylactic and therapeutic use of a murine anti-tumor necrosis factor monoclonal antibody in Escherichia coli sepsis in the rabbit.
OBJECTIVE
To determine the efficacy of a murine anti-tumor necrosis factor (TNF) monoclonal antibody in the treatment of Escherichia coli peritonitis and sepsis in the rabbit.


METHODS
Prospective, paired, randomized, blinded, controlled animal trial.


METHODS
Animal research laboratory.


METHODS
Male New Zealand white rabbits.


METHODS
Anesthetized rabbits were cannulated with indwelling femoral arterial and venous catheters. Peritonitis and sepsis were induced by intraperitoneal challenge using live E. coli O18ac bacteria. All animals were treated with gentamicin and ceftriaxone 1 hr after challenge. One group (prophylaxis experiment) consisting of ten rabbit pairs (the prophylaxis group), was treated with either murine anti-TNF monoclonal antibody or an equivalent volume of 5% albumin 3 hrs before E. coli challenge. A second group (therapeutic experiment) of 17 rabbit pairs, the treatment group, was also treated with murine anti-TNF monoclonal antibody or albumin control 1 hr after E. coli challenge.


RESULTS
All animals were bacteremic 1 hr after challenge. Physiologic measures of sepsis (heart rate, mean arterial pressure, serum bicarbonate, and arterial pH) did not differ between control, prophylaxis, and treatment groups. Peak serum TNF concentration was significantly (p < .01) lower in animals receiving anti-TNF monoclonal antibody, in both the prophylaxis and treatment groups, than in control animals. The survival rate was not improved significantly in either the prophylaxis or treatment group.


CONCLUSIONS
Prophylactic and therapeutic use of anti-TNF monoclonal antibody in a rabbit model of E. coli peritonitis and sepsis significantly lowers TNF concentrations but does not ameliorate the physiologic effects of sepsis and does not significantly improve survival.
Stack
A M
AM
Division of Emergency Medicine, Children's Hospital, Boston, MA, USA.
Saladino
R A
RA
Thompson
C
C
Sattler
F
F
Weiner
D L
DL
Parsonnet
J
J
Nariuchi
H
H
Siber
G R
GR
Fleisher
G R
GR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001639:Bicarbonates / Q000097:blood; D001794:Blood Pressure; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004927:Escherichia coli Infections / Q000188:drug therapy*; D008297:Male; D010538:Peritonitis / Q000188:drug therapy*; D011446:Prospective Studies; D011817:Rabbits; D011897:Random Allocation; D018805:Sepsis / Q000188:drug therapy*; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001639:Bicarbonates; D014409:Tumor Necrosis Factor-alpha