European Journal of Nutrition

, Volume 54, Issue 1, pp 129–138 | Cite as

Formula-feeding is associated with shift towards Th1 cytokines

  • Beate Winkler
  • Julia Aulenbach
  • Thomas Meyer
  • Armin Wiegering
  • Matthias Eyrich
  • Paul-Gerhardt Schlegel
  • Verena WiegeringEmail author
Original Contribution



Breast-feeding (BF) versus formula-feeding (FF) may be a factor for the development and differentiation of T-cell subsets and cytokine production in infancy and childhood. We therefore investigated T-cell subpopulations and their cytokine production by flow cytometry as well as cytokine levels in serum samples in breast-fed versus formula-fed infants and children.


Heparinised blood was taken from 191 healthy infants and children. Peripheral blood mononuclear cells were stimulated with phorbol-mystriate-acetate and ionomycin in the presence of brefeldin. T-cell subsets and cytokines were determined by flow cytometry. Furthermore, serum concentrations of IFNγ and IL4 were measured using ELISA. An IFNγ/IL4 ratio was calculated to estimate the Th1/Th2 balance.


Children who were formula-fed show higher numbers of memory T and T helper cells. After stimulation, the number of IFNγ-positive memory T-cells was increased up to the age of 6 years. Breast-fed infants show higher percentages of IL4-positive T helper cells. At ELISA determination, formula-fed children showed higher IFNγ levels than breast-fed children, while IL4 levels did not differ. The IFNγ/IL4 ratio (FACS and ELISA) was elevated in formula-fed infants and children.


This systematic analysis of cytokine profiles during childhood in dependency of BF allows a better understanding of immune maturation and demonstrates the influence of early feeding on immune function throughout childhood, even after cessation of BF. FF induces a shift towards Th1 cytokines in children. This may have an influence on the development of autoimmune disease in later life.


Breast-feeding Cytokines Th1/Th2 Flow cytometry 



Breast-fed children


Cluster of differentiation


Dendritic cells


Foetal calf serum


Formula-fed children


Fluorescein isothiocyanate


Human leucocyte antigen




Peripheral blood mononuclear cells






Transforming growth factor


T helper cell type 1


Regulatory T-cells





We thank the staff of the Outpatient Department as well as the technical staff of the stem cell processing unit at the University Children’s Hospital, Wuerzburg, for their excellent and dedicated patient care. This work was supported in part by an IZKF grant (to VW) and in part by the Tour of the Hope Foundation (to PGS).

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Beate Winkler
    • 1
  • Julia Aulenbach
    • 1
  • Thomas Meyer
    • 2
  • Armin Wiegering
    • 2
  • Matthias Eyrich
    • 1
  • Paul-Gerhardt Schlegel
    • 1
  • Verena Wiegering
    • 1
    Email author
  1. 1.Department of Paediatric Haematology/Oncology and Stem Cell TransplantationUniversity Children’s HospitalWürzburgGermany
  2. 2.Paediatric Surgery Unit, Department of General, Visceral, Vascular and Paediatric SurgeryUniversity of WuerzburgWürzburgGermany

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