PROCALCITONIN INCREASE AFTER ENDOTOXIN INJECTION IN NORMAL SUBJECTS

As procalcitonin concentrations have been shown to be elevated in pati ents with septicemia and gram-negative infections in particular, we pr oceeded to investigate the effect of endotoxin, a product of gramnegat ive bacteria, on procalcitonin concentrations in normal human voluntee rs. Endotoxin from Escherichia coli 0113:H10:k, was injected iv at a d ose of 4 mg/kg BW into these healthy volunteers. Blood samples were ob tained before and 1, 2, 4, 6, 8, and 24 h after injection of the endot oxin. Each patient's cardiovascular and overall clinical status was mo nitored over this period. The patients developed chills and rigors, my algia, and fever between 1-3 h. Tumor necrosis factor-cu levels increa sed sharply at 1 h and peaked at 90 min, reaching the baseline concent ration thereafter by 6 h. Interleukin-6 levels increased more graduall y, peaking at 3 h and reaching the baseline concentration at 8 h. The procalcitonin concentration, which was undetectable (<10 pg/mL) at 0, 1, and 2 h, was detectable at 4 h and peaked at 6 h, maintaining a pla teau through 8 and 24 h (4 ng/mL). There was no elevation of calcitoni n concentrations, which remained below 10 pg/mL, the lowest sensitivit y of the assay. Procalcitonin was measured by a two-antibody immunorad iometric assay specific for this peptide, with no cross-reactivity wit h calcitonin, katacalcin, or calcitonin gene-related peptide. We concl ude that endotoxin induces the release of procalcitonin systemically, that this increase is not associated with an increase in calcitonin, a nd that the increase in procalcitonin associated with septicemia in pa tients may be mediated through the effect of endotoxin described here. Whether procalcitonin participates in the mechanisms underlying infla mmation remains to be investigated.