Possible role of TNF on procalcitonin release in a baboon model of sepsis.
Procalcitonin (PCT) has been described as an early and discriminating marker of bacteria-associated sepsis in patients. However, little is known of its source and actions, especially with regard to its relation to tumor necrosis factor (TNF). TNF is responsible for the release of several other mediators of sepsis e.g., chemokines. We tested the hypothesis that plasma PCT levels during sepsis differ with regard to the degree of TNF availability. Severe hyperdynamic sepsis was induced in baboons (n = 14) by i.v. infusion of live E. coli (approximately 2 x 10(9) colony-forming units/kg) over 2 h. Animals were pretreated 2 h before E. coli either with 1 mg/kg humanized anti-TNF antibody (CDP571) or placebo (Ringer solution). Plasma PCT levels at baseline was barely detectable, but increased to about 4000 pg/mL at 4 h after E. coli infusion. Levels were maximal between 8 and 24 h and had returned nearly to baseline at 72 h. Although no TNF could be measured in the treated group, PCT levels were not different between the placebo and the TNF antibody treatment group. We conclude that PCT levels are not dependent on the systemic presence of TNF in an E. coli sepsis model in baboons. Such sepsis induced PCT release is clearly different from the previously reported PCT release during infusion of rhTNF in volunteers or chimpanzees.
Redl
H
H
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.
Schiesser
A
A
Tögel
E
E
Assicot
M
M
Bohuon
C
C
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002116:Calcitonin / Q000097:blood*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D008297:Male; D010215:Papio; D011498:Protein Precursors / Q000097:blood*; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D016207:Cytokines; D011498:Protein Precursors; D014409:Tumor Necrosis Factor-alpha; D002116:Calcitonin