Monoclonal antibody to endotoxin core protects mice from Escherichia coli sepsis by a mechanism independent of tumor necrosis factor and interleukin-6.
To study the role of cytokines as mediators of endotoxin-induced shock, the serum levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6) were compared in mice receiving either a monoclonal antibody to endotoxin core (clone 20), an irrelevant monoclonal antibody (A1), or culture media (DMEM/FCS) alone before lethal challenge with live Escherichia coli O111:B4. Clone 20 given 1.5 h before the bacterial challenge protected mice from death (mortality at 48 h 3% vs. 87%, P less than .001). The pattern of IL-6 release was indistinguishable in clone 20 recipients and controls: The area under the curve (AUC) for 5 h was 1.22 +/- 0.07 x 10(6), 1.03 +/- 0.17 x 10(6), and 1.22 +/- 0.07 x 10(6) units/ml for clone 20, A1, and DMEM/FCS, respectively. Similarly, the timing and extent of TNF release in the serum was virtually identical in clone 20 recipients that survived and control animals that died. AUC for 5 h was 30.8 +/- 4.0 x 10(3), 28.1 +/- 1.1 x 10(3), and 30.4 +/- 4.7 x 10(3) ng/ml in clone 20, A1, and DMEM/FCS recipients, respectively. Thus, TNF and IL-6 appear insufficient to cause death in this model of experimental gram-negative shock.
Department of Bacteriology, Hammersmith Hospital and Royal Postgraduate Medical School, London, United Kingdom.
A T
AT
Silva
B J
BJ
Appelmelk
W A
WA
Buurman
K F
KF
Bayston
J
J
Cohen
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004731:Endotoxins / Q000276:immunology*; D004927:Escherichia coli Infections / Q000209:etiology / Q000517:prevention & control*; D007116:Immunization, Passive; D015850:Interleukin-6 / Q000032:analysis* / Q000096:biosynthesis; D008297:Male; D051379:Mice; D012772:Shock, Septic / Q000209:etiology / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha