Procalcitonin and neopterin correlation with aetiology and severity of pneumonia
Introduction
Pneumonia is still the leading infectious disease cause of death.1 For early and effective treatment, consistent diagnosis is essential. Despite the availability of several diagnostic and therapeutic methods, a better and more specific prediction of sepsis is still needed. Even when a correct antibiotic treatment is set up, there are patients with a poor outcome. Not only anti-microbial but also immunomodulatory therapies can condition the clinical outcome and a multifaceted treatment approach is needed.2 Scoring systems primarily measure the physiological effect of the infection on the host, not the microbial and inflammatory mechanisms of the organ injury response. Early indicators of the degree of inflammatory response can aid in therapeutic decisions. Developing better methods to define high-risk septic populations for treatment with anti-inflammatory agents will increase the efficacy of this therapeutic approach and minimize its potential for harm.
Inflammatory response in lower respiratory tract is triggered by bacterial products as lipopolysaccharide or peptidoglican, which stimulate alveolar macrophages that produce cytokines, mainly IL-1, IL-6, IL-8 and TNF-α, as well as neutrophils recruitment.3, 4 The induced reactive nitrogen species as nitric oxide (NO) may play a role in the pathogenesis of acute lung injury.5 Cytokines have been tested with the purpose of measuring inflammatory response, but they are produced locally in the lung at the site of infection and they cannot be detected in serum in large amounts.6 This compartimentalized production of cytokines may explain why their serum detection is not useful as a diagnostic method. Only interleukin-6 can be found in serum in large amounts and it has been associated with pneumococcal pneumonia7, 8 and also as a prognostic factor in severe pneumonia.9 Nevertheless, cytokines undergo a fast down regulation in serum and interpretation of results is difficult. In addition, elevated plasma levels of several cytokines are found in different stages of acute respiratory distress syndrome.10, 11
Blood levels of acute phase proteins are thought to reflect closely the acute-phase protein synthesis by mediators of the local inflammatory process.12, 13, 14, 15, 16 Their increase in serum depends on cytokines stimulus, they have a longer half-life, they are more stable in vivo and ex vivo, and laboratory tests for their measurement are easy to perform. Procalcitonin (PCT), one of the calcitonin precursor peptides, has been reported as a sensitive marker of severe bacterial infection.12, 13 There is evidence to suggest that monocyte–macrophage system cells are capable of synthesizing PCT,14 as well as other non-thyroidal tissues, mostly parenchymal cells, under the stimulus of bacterial products.15 Neopterin is a 2-amino-4-OH-pteridine16 which is produced by monocytes/macrophages17 and monocyte-derived dendritic cells18 after induction by IFN-gamma that is secreted by T lymphocytes. It has been reported to act as a mediator of cell immunity against intracellular pathogens. Both parameters seem to be involved in regulation of inducible nitric oxide synthase (iNOS) during inflammation.19, 20, 21
The aim of our study was to evaluate the usefulness of procalcitonin (PCT) and neopterin in distinguishing among aetiologies as well as severity of inflammatory response in patients with pneumonia. Disease severity and organ injury were assessed by pneumonia severity index (PSI) and by the radiographic extent of the pneumonia.
Section snippets
Methods
The study population was adult patients admitted to Emergency Department presenting clinical signs of lower respiratory tract infection and a new infiltrate on the chest radiograph. The study was approved by the institutional ethics committee, and informed consent was signed by all the patients included. At the time of arrival to the Emergency, samples were collected for microbiological diagnosis: blood cultures, sputum or bronchial lavage specimens for culture, urine for antigen detection and
Results
Patients characteristics are described in Table 1. The mean age of the patients included in the study was 56.62 years (standard deviation 19.15, 95% confidence interval for mean 53.09–60.14).
Control group showed a mean PCT value of 0.35 ng/ml (standard deviation 0.048) and mean neopterin value of 0.28 (standard deviation 0.38). The distribution of the parameters in the different groups using median and 5–95 percentiles is described in Table 2. The values of PCT and neopterin in the different
Discussion
The aim of our study was to evaluate the usefulness of PCT and neopterin in distinguishing among aetiologies as well as severity in patients with pneumonia. The utility of PCT in the diagnosis of lower respiratory tract infection has been studied in prior reports, but its correlation with severity has been mostly evaluated in ventilator-associated pneumonia and acute respiratory distress syndrome. Fewer studies have assessed the value of the combined measurement of PCT and neopterin, and its
Acknowledgements
This study was supported by grant of ‘Sociedad Española de Neumología y Cirugía Torácica’ (SEPAR).
References (45)
The clinical features of severe community-acquired pneumonia presenting as septic shock. Norasept II Study Investigators
J Crit Care
(2000)- et al.
High serum procalcitonin concentrations in patients with sepsis and infection
Lancet
(1993) - et al.
Procalcitonin expression in human peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis-related cytokines in vitro
J Lab Clin Med
(1999) - et al.
Neopterin induces nitric oxide-dependent apoptosis in rat vascular smooth muscle cells
Immunobiology
(1998) - et al.
Legionella pneumophila pathogenesis and immunity
Semin Pediatr Infect Dis
(2002) - et al.
BAL neopterin: a novel marker for cell-mediated immunity in patients with pulmonary tuberculosis and lung cancer
Chest
(2001) - et al.
Procalcitonin, C-reactive protein and APACHE II score for risk evaluation in patients with severe pneumonia
Clin Microbiol Infect
(2002) - et al.
Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial
Lancet
(2004) Guidelines for the management of adults with community-acquired pneumonia
Am J Respir Crit Care Med
(2001)Advances in antimicrobial therapy for respiratory tract infections
Curr Opin Pulm Med
(2000)
Defense mechanisms of the respiratory tract
The role of cytokines in bacterial pneumonia: an inflammatory balancing act
Proc Assoc Am Physicians
Increased levels of nitrate and surfactant protein A nitration in the pulmonary edema fluid of patients with acute lung injury
Am J Respir Crit Care Med
Compartimentalized cytokine production within the human lung in unilateral pneumonia
Am J Respir Crit Care Med
Diagnostic and prognostic value of interleukin-6 and C-reactive protein in community-acquired pneumonia
Scand J Infect Dis
IL-1beta and IL-6 in community-acquired pneumonia: bacteremic pneumococcal pneumonia versus Mycoplasma pneumoniae pneumonia
Infection
Tumor necrosis factor-α and angiostatin are mediators of endothelial cytotoxicity in bronchoalveolar lavages of patients with acute respiratory distress syndrome
Am J Respir Crit Care Med
A role of vascular endothelial growth factor in acute and resolving lung injury
Am J Respir Crit Care Med
Procalcitonin—a new indicator of the systemic response to severe infections
Infection
Production of procalcitonin (PCT) in non-thyroidal tissue after LPS injection
Horm Metab Res
Neopterin: a review
Exp Dermatol
Modulation of neopterin formation and tryptophan degradation by Th1-and Th2-derived cytokines in human monocytic cells
Clin Exp Immunol
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