Procalcitonin increase after endotoxin injection in normal subjects.

Abstract

As procalcitonin concentrations have been shown to be elevated in patients with septicemia and gram-negative infections in particular, we proceeded to investigate the effect of endotoxin, a product of gram-negative bacteria, on procalcitonin concentrations in normal human volunteers. Endotoxin from Escherichia coli 0113:H10:k, was injected i.v. at a dose of 4 mg/kg BW into these healthy volunteers. Blood samples were obtained before and 1, 2, 4, 6, 8, and 24 h after injection of the endotoxin. Each patient's cardiovascular and overall clinical status was monitored over this period. The patients developed chills and rigors, myalgia, and fever between 1-3 h. Tumor necrosis factor-alpha levels increased sharply at 1 h and peaked at 90 min, reaching the baseline concentration thereafter by 6 h. Interleukin-6 levels increased more gradually, 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 plateau through 8 and 24 h (4 ng/mL). There was no elevation of calcitonin concentrations, which remained below 10 pg/mL, the lowest sensitivity of the assay. Procalcitonin was measured by a two-antibody immunoradiometric assay specific for this peptide, with no cross-reactivity with calcitonin, katacalcin, or calcitonin gene-related peptide. We conclude that endotoxin induces the release of procalcitonin systemically, that this increase is not associated with an increase in calcitonin, and that the increase in procalcitonin associated with septicemia in patients may be mediated through the effect of endotoxin described here. Whether procalcitonin participates in the mechanisms underlying inflammation remains to be investigated.

Are there new approaches for diagnosis, therapy guidance and outcome prediction of sepsis?

“…The peptide precursor is released by parenchymal cells including liver, kidney and muscles cells as well as adipocytes in response to bacterial toxins. After exposition to those toxins, serum levels of PCT increase within 2 to 4 h [20] and a peak of PCT in serum can be detected after approximately 14 h [21,22] . PCT is seen as a specific biomarker for bacterial infection [23] , although elevations of PCT in serum can also be observed under non-infectious conditions, such as trauma [24] , major surgical procedures, pancreatitis and renal impairment [25][26][27][28] .…”

Calcium-sensing Receptor Gene Transcription Is Up-regulated by the Proinflammatory Cytokine, Interleukin-1β

“…In addition, the serum concentra-tions of proinflammatory cytokines such as interleukin-1␤ (IL-1␤) and tumor necrosis factor-␣ (TNF-␣) are markedly increased in patients with burn injury or sepsis and are inversely related to the calcium concentration (16). Serum procalcitonin levels increase after endotoxin injection in normal human subjects (20).…”

Serum levels of interleukin‐6 may predict organ dysfunction earlier than SOFA score

“…The peak day in IL‐6 was significantly earlier than that in the SOFA score. Interleukin‐6 began to increase 1 h after the insult and then reach a peak after approximately 3–6 h 19, 20. Procalcitonin started to rise 3–4 h after the insult and peaked at 24 h 11, 20.…”

“…Interleukin‐6 began to increase 1 h after the insult and then reach a peak after approximately 3–6 h 19, 20. Procalcitonin started to rise 3–4 h after the insult and peaked at 24 h 11, 20. C‐reactive protein elevated at 4–6 h and peaked at 24–50 h 11, 21.…”