Procalcitonin as a marker of the systemic inflammatory response to infection

Abstract

K. R. has been reimbursed by B. R.A. H.M. S. Diagnostica GmbH, the manufacturer of procalcitonin, for organizing educational symposia, research projects, speaking, and consulting. M. M. has received funds for research and fees for speaking from B. R IntroductionSevere infections and sepsis are common causes of morbidity and mortality in intensive care units. Such conditions are accompanied by clinical and laboratory signs including changes in body temperature, leukocytosis, and tachycardia. However, these manifestations of systemic inflammation may be noninfectious in origin and are neither specific nor sensitive for sepsis. A similar inflammatory response occurs in patients suffering from pancreatitis [1], major trauma [2], and burns [3] without infectious complications. It is therefore frequently difficult to distinguish between patients in organ dysfunction or shock who have systemic infection and those who do not [4]. Bacteriological evidence of infection may not develop concurrently with clinical signs of sepsis. Positive bacteriological results may be due to contamination, and negative results do not exclude the presence of infection or sepsis. Since these standard clinical and laboratory parameters lack sensitivity and specificity, other markers are needed to provide an early indication of an infectious cause of a generalized inflammatory response, and thus allow early diagnosis and more specific therapeutic interventions. One such parameter, procalcitonin, has recently gained interest as a possible marker of the systemic inflammatory response to infection. Biology of procalcitoninProcalcitonin, a propeptide of calcitonin, is normally produced in the C-cells of the thyroid gland [5,6]. A specific protease cleaves procalcitonin to calcitonin, katacalcin, and an N-terminal residue [5]. Normally all the procalcitonin is cleaved, and none released into the bloodstream. Procalcitonin levels are therefore very low (< 0.1 ng/ml) in healthy humans. However, during severe infections with systemic manifestations procalcitonin levels increase to over 100 ng/ml. Remarkably, the large amounts of procalcitonin produced during infections do not lead to an increase in plasma calcitonin levels or activity [7]. In contrast to the short half-life of calcitonin (10 min), procalcitonin has a long half-life of approximately 22±35 h in serum [8,9].During severe systemic infections procalcitonin is probably produced by extrathyroid tissues. Patients who have previously undergone total thyroidectomy can still produce high levels of procalcitonin during a severe infectious episode [7]. The exact site of procalcitonin production during sepsis is uncertain. In a hamster model of sepsis procalcitonin mRNA was found in numerous tissues [10]. Studies in our laboratory have implicated mononuclear leukocytes [11]; endotoxin and sepsis-related proinflammatory cytokines had pronounced stimulatory effects on procalcitonin mRNA expression in human mononuclear leukocytes when measured by the reverse-transcriptase polymerase chain reaction. End...

Procalcitonin in Children with Escherichia coli O157:H7 Associated Hemolytic Uremic Syndrome

“…Severely increased PCT levels were noted in four patients with HUS on d 5 and 6 of enteritis (8,13,59, 125 g/L). One child had acute pancreatitis and presented with hallucinations (59 g/L), whereas another presented with convulsions and had particularly severe colitis (125 g/L).…”

“…Increased serum PCT levels have been noted in baboons or healthy adult volunteers treated with LPS (11,12). The serum half-life of PCT is approximately 24 h, which is longer than the proinflammatory cytokines TNF-␣ or IL-6 (12)(13)(14). Low concentrations of PCT are found in patients with noninfectious inflammatory processes (Ͻ1.0 -2.0 g/L) or viral infections (Ͻ0.5-1.0 g/L).…”

Procalcitonin as a Biomarker of Severity Degree in Sepsis Due to Pneumonia

“…Approximately one-third of human lymphocytes and monocytes unstimulated PCT protein which can be explained in immunology, this condition is triggered by bacterial LPS, but monocytes from patients with septic shock showed the increased basal values and the increase of PCT level stimulated by LPS. [8,23] Based on Table 7 shows that the sepsis severity affects on the increase of PCT level in patients with sepsis due to pneumonia. This is consistent to the research Elkhashab et al 2014 conducted at the Hospital of the University of Alexandria which obtained that the level of PCT increased in septic patients with pneumonia, with p = 0.002.…”

Plasma procalcitonin in rheumatic diseases

“…Nel 1993 fu descritta per la prima volta come proteina serica indotta da stati settici (2). Le prime pubblicazioni sull'argomento evidenziarono come la PCT fosse principalmente prodotta in corso d'infiammazione sistemica severa indotta da infezioni batteriche, mentre la sua concentrazione rimanesse bassa durante altri tipi d'infiammazione (ad esempio infezioni virali, malattie autoimmuni, rigetto da trapianto) (3). La fisiopatologia di tale molecola è ancora per gran parte oscura, così che poco se ne conosce della biochimica, dell'origine, dei meccanismi d'induzione e di un'eventuale funzione biologica (4).…”

“…I suoi livelli rimangono invece bassi quando un'infezione non porta ad una risposta infiammatoria sistemica. È stato inoltre dimostrato uno stretto legame sia con l'entità sia con la cronologia della risposta infiammatoria sistemica (3). In ragione di tali caratteristiche, la PCT è stata ritenuta un possibile ausilio nel monitoraggio del decorso della sindrome da risposta infiammatoria sistemica (SIRS) in corso di sepsi.…”