Systemic cytokines and chemokines on admission of children hospitalized with community-acquired pneumonia
Introduction
Community-acquired pneumonia (CAP) remains the main single cause of death and a frequent cause of hospital admissions in children under-5 years worldwide, with 1 million estimated deaths in 2015 and approximately 15 million estimated admissions in 2010 [1], [2].
It is currently very difficult to establish the etiological diagnosis of CAP. This is mostly due to lack of rapid tests with sensitivity and specificity high enough to be appropriately employed in emergency rooms or primary health-care settings, particularly among children [3]. Among the several putative etiological agents of childhood CAP, Streptococcus pneumoniae has been identified as the most common bacterial agent [3], [4]. Nevertheless, clinical and radiological parameters, as well as presently available laboratory biomarkers have been found to be useless to distinguish pneumococcal cases from non-pneumococcal cases [3], [5].
S. pneumoniae induces an intense inflammation in the lungs with the release of cytokines and chemokines from innate immunity. This process activates alveolar macrophages and systemic neutrophils to promote the clearance of pneumococcal strains [6], [7]. Some cytokines are recognized to play a pivotal role in innate defense against S. pneumoniae, such as tumor necrosis factor α (TNFα) and interleukin (IL)-1β, in the first moment of infection, being followed by IL-6, IL-8 and IL-10 [6], [7], [8].
Since the 1990’s, several studies have been searching for association between inflammatory cytokines and bacterial CAP in adults [9], [10]. Few other studies have investigated this issue among children, but none has presented a practical and useful conclusion so far [11], [12], [13]. Thus, we aimed to evaluate further if there was association between serum cytokineś or chemokineś levels on admission and pneumococcal infection among children hospitalized with CAP.
Section snippets
Study design
This was a prospective study conducted at the Emergency Room of the Federal University of Bahia Hospital, in Salvador, Northeast, Brazil, from September 2003 to May 2005. Every child aged <5 years hospitalized due to CAP was evaluated upon admission. The diagnosis was made by the pediatrician on duty. Diagnosis was based upon fulfillment of the following criteria: (1) respiratory complaints plus (2) fever or difficulty breathing plus (3) pulmonary infiltrates on the chest radiograph (CXR) taken
Study population
A total of 322 patients were evaluated, out of which 45 (14%) were excluded because they fulfilled one of the exclusion criteria. A further exclusion was due to serum sample unavailability for cytokine/chemokine measurement (n = 61) or undetected etiology (n = 50) (Fig. 1). Thus, the study group comprised 166 patients. Overall, the median (IQR) age was 17 (10–28) months. There were 98 (59.0%) boys. None had previously received either pneumococcal or influenza vaccines. On the contrary, 81% had
Discussion
In this study, IL-6 increase was identified as independently associated with pneumococcal infection among children under 5 years of age hospitalized with CAP. Additionally, we demonstrated that IL-6 levels under 12.5 pg/ml have high negative predictive value for pneumococcal infection among these patients. To the best of our knowledge, this is the first time that this association is reported with such evidence among children and the threshold of 12.5 pg/ml for IL-6 is found. As a matter of
Acknowledgements
We thank all families and patients who took part in this study and the staff of the Federal University of Bahia Hospital for their commitment to this investigation. Maria-Regina A. Cardoso, Aldina Barral, and Cristiana M. Nascimento-Carvalho are senior investigators at the Brazilian Council for Scientific and Technological Development (CNPq).
Funding
This study was supported by the Bahia State Agency for Research Funding (FAPESB) (grant no. PNX 0019/2009).
Role of the funding source
FAPESB had no role in study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the article for publication.
Conflicts of interests
None for all authors.
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