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Front. Pediatr. | doi: 10.3389/fped.2017.00255


  • 1University Children’s Hospital Basel, Switzerland
  • 2Department of Infectious Diseases, University of Amsterdam, Netherlands

Cytokines have attracted much attention as diagnostic biomarkers for infectious and inflammatory diseases in recent years. However, understanding of maturation and normal age-associated values is limited. This review summarizes evidence on the influence of age and other factors on expression profiles of soluble and intracellular cytokines in healthy children. IFN-γ, IL-6, IL-10 and TNF-α are the most frequently investigated cytokines, of which an age-associated increase was shown consistently for IFN-γ and TNF-α. An age-associated decrease of IL-13 was seen in resource-limited settings. For other cytokines including IL-1RA, IL-2 and IL-10 uni- or bimodal curves have been described, and results were influenced by study setting. To conclude, despite limited current understanding of the development of cytokine expression age clearly influences expression profiles in healthy children. Dynamics of cytokine expression in childhood need to be considered when these are measured in diagnostic assays or as biomarkers. In addition, cytokine-targeting agents may require adjustment for normal values when used in children.

Keywords: Cytokine expression, gender, Children, Infant, Adolescent, Sex, age influence

Received: 05 Oct 2017; Accepted: 15 Nov 2017.

Edited by:

Christian M. Hedrich, Institute of Translational Medicine, University of Liverpool, United Kingdom

Reviewed by:

Klaus Tenbrock, RWTH Aachen University, Germany
Christoph Kessel, University Hospital Muenster, Department for Pediatric Rheumatology & Immunology, Germany
Hermann Girschick, Vivantes Klinikum, Germany  

Copyright: © 2017 Decker, Ritz and Grobusch. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: MD, PhD. Nicole Ritz, University Children’s Hospital Basel, Basel, Switzerland,