Tumor necrosis factor (TNF)-dependent shedding of the p55 TNF receptor in a baboon model of bacteremia.
We have tested the hypothesis that the tumor necrosis factor (TNF) plays a significant role in vivo in TNF receptor shedding and studied the release of TNF-binding protein 1 (TNF-BP1), the soluble fragment of the 55- to 60-kDa TNF alpha (TNF) receptor, in a baboon model of Escherichia coli bacteremia, using three different doses of bacteria in acute infection (8 h) experiments (n [animals] = 11) and a single dose in a subchronic infection (72 h) experiment. In the subchronic infection study, one group of animals (n = 6) was pretreated with a neutralizing murine monoclonal antibody to TNF (CB0006). Concentrations of TNF and TNF-BP1 in plasma were determined in specific, monoclonal antibody-based immunoassays. Untreated animals (n = 6) showed undetectable TNF concentrations (< 10 pg/ml at baseline), whereas TNF-BP1 levels in plasma were in the range of 2 ng/ml, similar to concentrations observed in humans. Infusion of bacteria resulted in a rapid, dose-dependent increase in plasma TNF concentrations that reached a maximal level after 2 h and returned to baseline within 6 h. TNF-BP1 concentrations also showed a dose-dependent increase to peak concentrations three- to fivefold above baseline within 2 h but, in contrast to TNF levels, remained significantly elevated for up to 48 h. In animals pretreated with antibody CB0006, circulating TNF was completely neutralized, and TNF-BP1 was significantly reduced. We conclude that TNF-BP1 is released in bacteremia and that release in vivo is partially dependent on the presence of TNF.
Redl
H
H
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.
Schlag
G
G
Adolf
G R
GR
Natmessnig
B
B
Davies
J
J
D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD; D016470:Bacteremia / Q000378:metabolism*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000378:metabolism*; D008297:Male; D009500:Neutralization Tests; D010215:Papio; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D012772:Shock, Septic / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha