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Published on: October 13, 2017
Age-related changes in intracellular cytokine expression in healthy children
Verena Wiegering1, Matthias Eyrich, Christian Wunder
1Department of Pediatrics, Pediatric Hematology, Oncology and Stem Cell Transplantation program, University Children's Hospital Wuerzburg, Germany. Wiegering_V@klinik.uni-wuerzburg.de
Insights
This study reveals how cytokine production in children changes with age and sex. Key findings show shifts in Interleukin-2 (IL-2), Interferon-gamma (IFN-γ), and Tumor Necrosis Factor-alpha (TNF-α) levels, impacting immune maturation understanding.
Area of Science:
- Immunology
- Pediatric Health
- Cellular Biology
Background:
- Cytokine production is crucial for immune responses.
- Understanding normal cytokine profiles in children is essential for diagnosing immune disorders.
- Previous research has not comprehensively detailed age- and sex-dependent cytokine expression in pediatric populations.
Purpose of the Study:
- To establish normative values for intracellular cytokine expression in healthy children aged 0-18 years.
- To investigate the impact of age and sex on cytokine profiles in pediatric lymphocytes.
- To provide a baseline for interpreting cytokine data in pediatric pathological conditions.
Main Methods:
- Flow cytometry was used to analyze intracellular cytokine production in 117 healthy children's lymphocytes.
- Samples were stimulated in vitro with PMA, ionomycin, and brefeldin for 24 hours.
- Intracellular anti-cytokine antibodies and surface antibodies were used for staining.
Main Results:
- Interleukin-2 (IL-2) expression decreased with age, while Interferon-gamma (IFN-γ) and Tumor Necrosis Factor-alpha (TNF-α) increased.
- Interleukin-4 (IL-4), Ki67, and Transforming Growth Factor-beta (TGF-β) levels remained stable across age groups.
- Cytokines were primarily produced by memory T-cells.
- Sex-based differences were observed: younger boys (<6 years) showed higher IL-2 production, and older girls (>12 years) exhibited greater IFN-γ production compared to boys.
Conclusions:
- Cytokine production in healthy children undergoes significant age- and sex-dependent maturation.
- These findings provide critical reference ranges for pediatric immune assessment.
- This study enhances the interpretation of cytokine profiles in children with various health conditions.
Abstract:
Cytokine production by human lymphocytes from healthy children (ages 0-18 years) was assessed using a flow cytometric procedure involving staining of intracellular cytokines by the paraformaldehyde-saponin procedure. To establish valid cytokine values for intracellular cytokine expression in healthy children in the different age groups, we measured 117 samples after 24 h in vitro stimulation with PMA, ionomycin and brefeldin followed by staining with intracellular anti-cytokine and surface antibodies. We found decreasing IL-2 expression, increasing IFN-gamma and TNF-alpha production and stable IL-4, Ki67 and TGFb levels with advancing age. The cytokines were mainly produced by memory T-cells. Apart from age, there was a differential expression in boys and girls: boys (< 6 years) produce significantly more IL-2 (p < 0,04), while girls > 12 years produce more IFNg than boys of the same age (p < 0.05). This systematic analysis of cytokine profiles during childhood allows a better understanding of immune maturation and will contribute significantly to the interpretation of cytokine data from children with pathological conditions.
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