Elsevier

Cytokine

Volume 107, July 2018, Pages 1-8
Cytokine

Systemic cytokines and chemokines on admission of children hospitalized with community-acquired pneumonia

https://doi.org/10.1016/j.cyto.2017.11.005Get rights and content

Abstract

Community-acquired pneumonia (CAP) is the main cause of death in children under-5 years worldwide and Streptococcus pneumoniae is the most common bacterial agent. However, it is difficult to identify pneumococcal infection among children with CAP. We aimed to assess association between any cytokine/chemokine and pneumococcal infection in childhood CAP. Furthermore, we evaluated the diagnostic value of cytokine/chemokine for pneumococcal infection. This prospective study was conducted at an Emergency Room, in Salvador, Brazil. Children <5-years-old hospitalized with CAP in a 21-month period were evaluated. On admission, clinical and radiological data were collected along with biological samples to investigate 20 etiological agents and determine serum cytokines (interleukin (IL)-8, IL-6, IL-10, IL-1β, IL-12, TNF-α, IL-2, IL-4, IL-5, γ-interferon), and chemokines (CCL2, CCL5, CXCL9, CXCL10) concentration. From 166 patients with etiology detected, pneumococcal infection was detected in 38 (22.9%) cases among which the median IL-6(pg/ml) was 31.2 (IQR: 12.4–54.1). The other 128 cases had other causative agents detected (Haemophilus influenzae, Moraxella catarrhalis, atypical bacteria and viruses) with the median IL-6 concentration being 9.0 (IQR: 4.1–22.0; p < 0.001). The area under the ROC curve for IL-6 to predict pneumococcal CAP was 0.74 (95%CI: 0.65–0.83; p < 0.001). By multivariate analysis, with pneumococcal CAP as dependent variable, IL-6 was an independent predictor for pneumococcal infection (OR = 5.56; 95%CI: 2.42–12.75, cut-off point = 12.5 pg/ml; p = 0.0001). The negative predictive value of IL-6 under 12.5 pg/ml for pneumococcal infection was 90% (95%CI: 82–95%). Independently significant difference was not found for any other cytokines/chemokines. Serum IL-6 concentration on admission is independently associated with pneumococcal infection among children under-5 years hospitalized with CAP.

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.

References (34)

  • S.H. Gillespie et al.

    Pathogenesis of pneumococcal infection

    J. Med. Microbiol.

    (2000)
  • D. Lieberman et al.

    IL-1β and IL-6 in community-acquired pneumonia: bacteremic pneumococcal pneumonia versus Mycoplasma pneumoniae pneumonia

    Infection

    (1997)
  • M. Christ-Crain et al.

    Clinical review: the role of biomarkers in the diagnosis and management of community-acquired pneumonia

    Crit. Care

    (2010)
  • P. Toikka et al.

    Serum procalcitonin, C-reactive protein and interleukin-6 for distinguishing bacterial and viral pneumonia in children

    Pediatr. Infect. Dis. J.

    (2000)
  • G. Tumgor et al.

    Aetiological agents, interleukin-6, interleukin-8 and CRP concentrations in children with community- and hospital-acquired pneumonia

    Ann. Trop. Paediatr.

    (2006)
  • I.C. Michelow et al.

    Systemic cytokine profile in children with community-acquired pneumonia

    Pediatr. Pulmonol.

    (2007)
  • C.M. Nascimento-Carvalho et al.

    The role of respiratory viral infections among children hospitalized for community-acquired pneumonia in a developing country

    Pediatr. Infect. Dis. J.

    (2008)
  • Cited by (0)

    View full text