In vitro cow's milk protein-specific inflammatory and regulatory cytokine responses in preterm infants with necrotizing enterocolitis and sepsis

Pediatr Res. 2011 Feb;69(2):165-9. doi: 10.1203/PDR.0b013e31820263e7.


Enteral feeding with cow's milk formula is associated with neonatal necrotizing enterocolitis (NEC) and sepsis. Dietary antigen sensitization may play a role in promoting and/or sustaining inflammation in both conditions. Aiming at investigating cow's milk protein (CMP)-specific cytokine responses in preterm infants with NEC and sepsis, 14 babies with NEC, 14 matched healthy controls, and 10 septic controls were recruited. Unstimulated and stimulated peripheral blood mononuclear cells (PBMCs) secreting IFN-γ, IL-4, IL-10, and TGF-β1 were counted by the single-cell enzyme-linked immunospot (ELISPOT) assay. During the acute phase of NEC, patients showed a general pattern of a high level of cytokine secretion both when unstimulated and stimulated by mitogen [phytohaemagglutinin (PHA)] and CMPs: beta-lactoglobulin (β-lg) and casein. These responses were more marked to β-lg for IFN-γ, IL-4, and IL-10 than TGF-β1. Cytokine responses in sepsis were lower than in NEC (lowest in healthy controls, with a minimal TGF-β1 response). At term, lower frequencies of cytokine-secreting cells were elicited than during the acute phase, except for TGF-β1 secreting cells, which increased at term (in response to PHA and CMPs) particularly following not only NEC but also sepsis.

MeSH terms

  • Case-Control Studies
  • Caseins / immunology
  • Cells, Cultured
  • Cytokines / metabolism*
  • Enterocolitis, Necrotizing / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Inflammation Mediators / metabolism*
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-4 / metabolism
  • Lactoglobulins / immunology
  • Leukocytes, Mononuclear / immunology*
  • Male
  • Milk Proteins / immunology*
  • Sepsis / immunology*
  • Transforming Growth Factor beta1 / metabolism


  • Caseins
  • Cytokines
  • IL10 protein, human
  • IL4 protein, human
  • Inflammation Mediators
  • Lactoglobulins
  • Milk Proteins
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma