Protection with antibody to tumor necrosis factor differs with similarly lethal Escherichia coli versus Staphylococcus aureus pneumonia in rats.
BACKGROUND
Differing factors may alter the effects of antibody to tumor necrosis factor (TNF) in infection and sepsis. The authors tested whether bacteria type or treatment route alters antibody to TNF in a rat model of bacterial pneumonia.


METHODS
Rats (n = 231) received similarly lethal doses of either intratracheal Escherichia coli or Staphylococcus aureus followed by treatment with either intratracheal or intraperitoneal antibody to TNF or control serum. Animals received antibiotics (cefotiam daily dose, 100 mg/kg) starting 4 h after inoculation and were studied for up to 96 h.


RESULTS
Compared with S. aureus, E. coli increased serum TNF and interleukin-6 concentrations, lung lavage TNF concentrations, neutrophil counts, and alveolar-to-arterial oxygen gradients and decreased circulating neutrophils and lymphocytes (P > or = 0.05 for all). Compared with controls, with both bacteria, except for lung lavage TNF concentrations (which decreased with intratracheal but not with intraperitoneal antibody to TNF), treatment route did not alter the effects of antibody to TNF on any parameter (P = not significant for all). Antibody to TNF reduced mortality rates (relative risk of death +/- SEM) with both E. coli (-1.6 +/- 0.6; P = 0.006) and S. aureus (-0.5 +/- 0.04; P = 0.185), but these reductions were greater with E. coli than with S. aureus in a trend approaching statistical significance (P = 0.09). Compared with controls, similarly (P = not significant) with both bacteria, antibody to TNF decreased lung lavage and tissue bacteria concentrations (both P < 0.05) and serum TNF concentration (P < 0.09) and increased circulating neutrophils and lymphocytes (both P < or = 0.01). Compared with S. aureus, with E. coli antibody to TNF decreased alveolar-to-arterial oxygen gradients (P = 0.04) and increased serum interleukin-6 concentrations (P = 0.003).


CONCLUSIONS
Antibody to TNF improved host defense and survival rates with both lethal E. coli and S. aureus pneumonia, but protection was greater with E. coli, where TNF concentrations were higher than with S. aureus. The efficacy of antiinflammatory agents in sepsis may be altered by bacteria type.
Karzai
Waheedullah
W
Department of Anesthesiology and Intensive Care Medicine, University Hospital, Jena, Germany. w.karzai.ana@zentralkinik-bad-berka.de
Cui
Xizhong
X
Mehlhorn
Bjoern
B
Straube
Eberhard
E
Hartung
Thomas
T
Gerstenberger
Eric
E
Banks
Steven M
SM
Natanson
Charles
C
Reinhart
Konrad
K
Eichacker
Peter Q
PQ
D000280:Administration, Inhalation; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015310:Cefotiam / Q000627:therapeutic use; D002511:Cephalosporins / Q000627:therapeutic use; D004926:Escherichia coli / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000097:blood; D007442:Intubation, Intratracheal; D007958:Leukocyte Count; D018655:Lymphocyte Count; D008297:Male; D009504:Neutrophils / Q000276:immunology; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000502:physiology; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D011023:Pneumonia, Staphylococcal / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000276:immunology; D013211:Staphylococcus aureus / Q000472:pathogenicity; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D002511:Cephalosporins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D015310:Cefotiam; D010100:Oxygen