Abstract

BackgroundChildren in low and middle-income countries have a high burden of pneumonia. Measuring the cytokine responses may be useful to identify novel markers for diagnosing, monitoring, and treating pneumonia.ObjectiveTo describe and compare a wide range of inflammatory mediators in plasma from children with WHO-defined severe and non-severe community acquired pneumonia (CAP), and explore to what extent certain mediators are associated with severity and viral detection.MethodsWe collected blood samples from 430 children with severe (n = 43) and non-severe (n = 387) CAP. Plasma from these children were analysed for 27 different cytokines, and we measured the association with age, disease severity and viral detection.ResultsThere were generally higher plasma concentrations of several cytokines with both pro-inflammatory and anti-inflammatory effects among children with severe CAP than in children with non-severe CAP. We found significantly higher concentrations of interleukin (IL)-1, IL-4, IL-6, IL-8, IL-9, IL-15, eotaxin, basic fibroblast growth factor (b-FGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-α) in the group of severe CAP. Most of these associations persisted when adjusting for age in linear regression analyses. The cytokine response was strongly associated with age but to a lesser extent with viral etiology.ConclusionThe plasma concentrations of several cytokines, both with pro-inflammatory and anti-inflammatory effects, were higher among children with severe illness. In particular G-CSF and IL-6 reflected severity and might provide complementary information on the severity of the infection.Trial registrationClinicalTrials.gov NCT00148733

Highlights

  • The burden of community-acquired pneumonia (CAP) in children is substantial in low- and middle-income countries

  • We found significantly higher concentrations of interleukin (IL)-1, IL-4, IL-6, IL-8, IL-9, IL-15, eotaxin, basic fibroblast growth factor (b-FGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-α) in the group of severe CAP

  • One study on cytokine profile and pandemic influenza H1N1 2009 virus infection in paediatric patients with pneumonia demonstrated that the concentration of interferon gamma inducible potein-10 (IP-10) and IL-6 concentrations were proportional to the severity of the infection defined by lymphopenia and hypoxia [6]

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Summary

Introduction

The burden of community-acquired pneumonia (CAP) in children is substantial in low- and middle-income countries. The cytokine responses in CAP have been explored mostly in adults and only a few studies have examined the cytokine response in young children with respiratory infections. One study in children with CAP found that systemic IL-6 was elevated and associated with markers of severity measured by white blood cell-band- forms, elevated procalcitonin and unequivocal consolidation [5]. One study on cytokine profile and pandemic influenza H1N1 2009 virus infection in paediatric patients with pneumonia demonstrated that the concentration of interferon gamma inducible potein-10 (IP-10) and IL-6 concentrations were proportional to the severity of the infection defined by lymphopenia and hypoxia [6]. Children in low and middle-income countries have a high burden of pneumonia. Measuring the cytokine responses may be useful to identify novel markers for diagnosing, monitoring, and treating pneumonia

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