Possible role of TNF on procalcitonin release in a baboon model of sepsis

Procalcitonin (PCT) has been described as an early and discriminating marke r of bacteria-associated sepsis in patients. However, little is known of it s source and actions, especially with regard to its relation to tumor necro sis factor (TNF). TNF is responsible for the release of several other media tors of sepsis e.g., chemokines. We tested the hypothesis that plasma PCT l evels during sepsis differ with regard to the degree of TNF availability. S evere hyperdynamic sepsis was induced in baboons (n = 14) by i.v. infusion of live E. coli (congruent to2 x 10(9) colony-forming units/kg) over 2 h. A nimals were pretreated 2 h before E. coli either with 1 mg/kg humanized ant i-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 af ter E. coli infusion. Levels were maximal between 8 and 24 h and had return ed nearly to baseline at 72 h. Although no TNF could be measured in the tre ated group, PCT levels were not different between the placebo and the TNF a ntibody treatment group. We conclude that PCT levels are not dependent on t he systemic presence of TNF in an E. coli sepsis model in baboons. Such sep sis induced PCT release is clearly different from the previously reported P CT release during infusion of rhTNF in volunteers or chimpanzees.