What Is Procalcitonin?
Procalcitonin (PCT) belongs to a distinct class of molecules known as hormokines due to its hormonal origin and the inflammation-related functions of its propeptides. PCT is a substance that comes before the hormone calcitonin in the body. Calcitonin helps maintain the balance of calcium in our bodies. PCT is made up of three smaller parts, and these parts can be found in the blood of healthy individuals. While calcitonin only lasts about ten minutes in the body, PCT has a much longer lifespan of around 25 to 30 hours.
PCT is produced mainly by special cells in the thyroid called parafollicular cells (C cells). It is also produced by neuroendocrine cells in the lungs and intestine. The production of PCT comes from a gene called calcitonin I (CALC-1), located on chromosome 11. During bacterial infections, the CALC-1 gene becomes more active, and PCT production increases in different tissues, not just the thyroid. However, when there is no infection, the CALC1 gene is inactive outside the thyroid. This means that during an infection, the detectable PCT in the blood is not produced by the thyroid's C cells but by the neuroendocrine cells in the lungs or intestine.
How Do PCT Levels Change in Infectious Diseases?
PCT can act like a hormone or a substance similar to cytokines, which are molecules involved in inflammation. The factors that control the production of these hormone-like substances have yet to be fully understood. They can be triggered directly by toxins released by harmful microbes or indirectly by the body's immune response through substances present in the blood or cells.
When something triggers a response in the body, PCT levels can be detected in the bloodstream within a few hours. They reach their highest levels within 12 to 24 hours and then gradually decrease over the next day.
What Is the Use of PCT as a Biomarker for Infectious Diseases?
Recent advances in biotechnology and genome sequencing have provided opportunities to enhance our understanding of critical illnesses and injuries. Early detection of infection is crucial as it enables timely preventive and therapeutic measures. Procalcitonin has shown promise as a marker for diagnosing bacterial infections since higher levels are observed in severe bacterial infections compared to viral infections and nonspecific inflammatory diseases. This makes PCT a valuable tool in supporting clinical decisions regarding initiating or discontinuing antibiotic therapy. The clinical utility of serum PCT levels is still evolving and continues to be investigated.
The use of PCT should be embedded in clinical algorithms tailored to the specific type of infection and clinical context. Optimal PCT level cutoffs have been established for certain infections and clinical settings, but only observational studies are available for others. Therefore, the clinical benefits and safety of using PCT require further definition.
PCT differs from calcitonin in terms of its biological activities. During severe systemic inflammation and bacterial infections, PCT levels notably increase and remain elevated until recovery. In contrast, PCT levels generally do not rise significantly in response to viral infections, suggesting its potential to distinguish between bacterial and viral infections. PCT has demonstrated utility in monitoring bacterial infections and aiding the differential diagnosis of systemic inflammatory response syndrome.
What Are the Clinical Applications of PCT?
PCT has demonstrated clinical usefulness in several applications. Healthcare professionals use it to guide empirical antibacterial therapy in patients with acute exacerbations of chronic bronchitis, community-acquired pneumonia (CAP), and sepsis. In conjunction with clinical parameters, PCT levels can help determine the effectiveness of empirical antibacterial therapy. Sequential PCT measurements can be employed to determine the discontinuation of antibacterial therapy.
The correlation between PCT levels and the severity of sepsis has been well established. PCT is superior to other biomarkers in diagnosing sepsis and correlates with microbial invasion's extent and severity. Additionally, PCT has shown promise in guiding antibiotic therapy in respiratory tract infections and other infections, aiding in distinguishing bacterial from non-bacterial infections.
PCT can play a role in antibiotic stewardship, essential for combating antimicrobial resistance. Algorithms based on PCT cutoff ranges have been developed to guide antibiotic treatment decisions. Several studies have shown that using sequential PCT levels can significantly reduce the duration of antibiotic therapy. PCT also has potential applications in resolving the etiology of fever in patients of unknown origin and as a marker of the host inflammatory response.
What Are the Drawbacks of PCT as a Biomarker in Infectious Diseases?
Despite its promising potential, there are limitations to using PCT as a marker of infection and sepsis. Nonspecific elevations in PCT levels can occur in situations of stress, trauma, surgery, or other nonbacterial systemic inflammation.
What Is the Role of PCT as a Prognosis Marker for Infectious Diseases?
PCT has emerged as a potential prognostic marker for infectious diseases. Numerous studies have consistently shown that elevated PCT levels in patients with infectious diseases are associated with worse outcomes and increased mortality rates. PCT can be valuable for differential diagnosis, prognosis assessment, and monitoring of critically ill patients. In infectious diseases, higher PCT levels often correlate with the severity of the condition. Additionally, a rising trend in PCT levels may indicate that the infection is poorly controlled, highlighting the need for improved management strategies. A significant study highlighted the importance of PCT measurements, revealing that high maximum PCT levels and daily PCT increase independently predict adverse outcomes within a specified timeframe. Serial monitoring of PCT levels is suggested to evaluate the host response to infection and the effectiveness of treatment. Some studies suggest that reducing PCT levels by more than 30 % of the initial value after the first 24 hours of antibacterial treatment indicates successful infection control and favorable treatment outcomes.
Conclusion:
Various tissues and organs produce PCT in response to pathogenic bacteria, fungi, and certain parasites.PCT is a widely evaluated marker that holds promise for diagnosing bacterial infections, differentiating between infectious and sterile causes of systemic inflammation, and assessing the severity of bacterial infections. However, the use of PCT is considered within the clinical context and considers various patient and therapy-related factors that may affect its levels. Further research is needed to fully understand the potential of PCT and its optimal application in clinical practice.
