Based on available data, the measurement of serum ProCT has definite utility as a marker of severe systemic inflammation, infection, and sepsis. However, publications concerning its diagnostic and prognostic utility are contradictory. In addition, patient characteristics and clinical settings vary markedly, and the data have been difficult to interpret and often extrapolated inappropriately to clinical usage. Furthermore, attempts at meta-analyses are greatly compromised by the divergent circumstances of reported studies and by the sparsity and different timing of the ProCT assays. Although a high ProCT commonly occurs in infection, it is also elevated in some noninfectious conditions. Thus, the test is not a specific indicator of either infection or sepsis. Moreover, in any individual patient, the precipitating cause of an illness, the clinical milieu, and complicating conditions may render tenuous any reliable estimations of severity or prognosis. It also is apparent that even a febrile septic patient with documented bacteremia may not necessarily have a serum ProCT that is elevated above the limit of functional sensitivity of the assay. In this regard, the most commonly applied assay (i.e., LUMItest) is insufficiently sensitive to detect potentially important mild elevations or trends. Clinical studies with a more sensitive ProCT assay that is capable of rapid and practicable day-to-day monitoring are needed and shortly may be available. In addition, investigations showing that ProCT and its related peptides may have mediator relevance point to the need for evaluating therapeutic countermeasures and studying the pathophysiologic effect of hyperprocalcitonemia in serious infection and sepsis.

No abstract

The worldwide yearly mortality from sepsis is substantial, greater than that of cancer of the lung and breast combined. Moreover, its incidence is increasing, and its response to therapy has not appreciably improved. In this condition, the secretion of procalcitonin (ProCT), the prohormone of calcitonin, is augmented greatly, attaining levels up to thousands of fold of normal. This hypersecretion emanates from multiple tissues throughout the body that are not traditionally viewed as being endocrine. The serum values of ProCT correlate with the severity of sepsis; they recede with its improvement and worsen with exacerbation. Accordingly, as highlighted in this review, serum ProCT has become useful as a biomarker to assist in the diagnosis of sepsis, as well as related infectious or inflammatory conditions. It is also a useful monitor of the clinical course and prognosis, and sensitive and specific assays have been developed for its measurement. Moreover, it has been demonstrated that the administration of ProCT to septic animals greatly increases mortality, and several toxic effects of ProCT have been elucidated by in vitro experimental studies. Antibodies have been developed that neutralize the harmful effects of ProCT, and their use markedly decreases the symptomatology and mortality of animals that harbour a highly virulent sepsis analogous to that occurring in humans. This therapy is facilitated by the long duration of serum ProCT elevation, which allows for a broad window of therapeutic opportunity. An experimental groundwork has been established that suggests a potential applicability of such therapy in septic humans.

These results demonstrate that increased ProCT exacerbates mortality in experimental sepsis, whereas neutralization of ProCT increases survival. Thus, ProCT, in addition to being an important marker of severity of systemic inflammation and mortality, is an integral part of the inflammatory process and directly affects the outcome.

In critically ill patients with sepsis, markedly elevated circulating calcitonin precursors might play a role in the development of the pronounced hypocalcemia. The specific calcitonin precursor(s) responsible for this effect and the pathophysiological mechanism remain to be elucidated.

These data from a large-animal model with polymicrobial sepsis demonstrate the salutary effect of early immunoneutralization of calcitonin precursors on physiologic and metabolic variables. Immunologic blockade of calcitonin precursors may offer a novel therapeutic approach to human sepsis.

No abstract

Our data show the utility of a rapid and sensitive assay for CTpr combined with interleukin-8 as a highly sensitive and specific diagnostic marker of bacterial sepsis in febrile, neutropenic children. The use of these markers as a clinical tool may allow for better prognostication for clinicians and may eventually lead to more targeted therapies for this heterogeneous population.