In this issue of the journal, Steinwald et al [1] extend limited clinical studies and report an animal
experiment showing that calcitonin precursors (predominantly procal-citonin)
are elevated in proportion to the severity of bacterial sepsis. They conclude
that procalcitonin, the major calcitonin precursor, is a good indicator of the
activity and severity of the inflammatory response and may be used for
monitoring bacterial infections.In recent years, a variety of laboratory and immunologic parameters
have been proposed as possible indicators of severe inflammatory response to
infections. One such parameter is procalcitonin, which has emerged as a
possible marker of severe generalized infections [2]. The
exact role of procalcitonin during infection is unclear. The elevated amount
found during sepsis does not lead to increased levels of calcitonin and there
is, as yet, no evidence that it may be involved in calcium metabolism. Also,
its exact site of production during sepsis is unclear; however, recent research
suggests that the monocytes may be one possible source during sepsis. Despite
the unknown (and potentially very important) patho-physiology of procalcitonin
during sepsis, much clinical research has focused on using procalcitonin as a
marker of the inflammatory response to severe generalized infections.Why is it important to have markers of infection? Although a recent
concensus conference has set up new definitions and diagnostic criteria of
sepsis, two major problems remain. First, uncontrolled infections are not the
only cause of systemic inflammation and other stimuli such as pancreatitis,
major trauma, and thermal injury can also trigger a systemic inflammatory
response. In the clinic, therefore, it is frequently difficult to decide on the
aetiology of an inflammatory response syndrome and direct appropriate therapy.
Second, the disappointing results of immunomodulatory trials in septic patients
have raised doubts as to whether conventional clinical and laboratory criteria
used for recruiting septic patients may suffice in identifying groups of
patients who would most likely benefit from such therapies [3]. Because of these problems, parameters that could provide
early information on the aetiology and severity of an inflammatory response
would be of interest. Such (a) marker(s) could also help target the populations
of septic patients who would benefit from immunomodulatory trials.Clinical data suggest that, whereas non-infectious inflammatory
stimuli and viral infections produce only minor increases in procalcitonin
levels, generalized bacterial infections produce large increases that seem to
reflect the severity of the infection [2,4]. Procalcitonin has been used to differentiate infectious
from non-infectious pancreatitis, infectious from non-infectious aetiology of
acute lung injury, and in differentiating transplant rejection from infectious
complications after organ transplantation.However, although procalcitonin offers considerable advantages in
comparison to conventionally used laboratory monitoring parameters, it does not
fulfil all the criteria of an ideal marker of severe microbial infections.
Procalci-tonin may not or may only slightly increase when infection remains
confined to a tissue or organ with no systemic manifestations. This may be one
of the reasons why calci-tonin precursor levels in Steinwald's study are very
similar in controls and less severe septic animals. Therefore, very low levels
of procalcitonin after the treatment of infection do not always indicate
complete eradication of the infection, and continuation of antibiotic therapy
or surgical measure may be necessary until all clinical signs of infection have
disappeared. Furthermore, procalcitonin levels may also be elevated after major
trauma or surgery, after cardiopulmonary bypass, and in patients with C-cell
carcinoma of the thyroid gland and small-cell carcinoma of the lung [4].Other important questions pertaining to procalcitonin remain
unanswered. Is procalcitonin release related to bacterial products (alone) or
do cytokines also play a role? Which cells produce procalcitonin during severe
infection? What specific endocrinologic or immunologic (dys)func-tion does
procalcitonin serve during severe infections? Because of these unanswered
questions and limitations, more clinical and laboratory studies are needed to
uncover the nature of this parameter in inflammatory states.