Evidence for Involvement of IL-9 and IL-22 in Cows' Milk Allergy in Infants

Nutrients. 2017 Sep 21;9(10):1048. doi: 10.3390/nu9101048.

Abstract

Although allergic inflammation is characterized by a T helper (Th) 2-dominant immune response, the discovery of a role for new T cell subsets in inflammatory diseases has added an additional layer of complexity to the understanding of the pathogeneses of allergic diseases. We evaluated plasma cytokine profiles in infants with cows' milk allergy (CMA), who were being treated with an elimination diet. In a prospective, randomized and controlled study, infants (aged 8.4 ± 3.9 months) with CMA were treated with an elimination diet for 120 days, which replaced cows' milk with a hydrolysed soy protein formula (n = 26) or a free amino acid formula (n = 20). Blood samples were collected before treatment during active disease (T0) and after 120 days, when symptoms were absent (T1). Plasma cytokine concentrations were measured. Infants with CMA had higher plasma concentrations of interleukin (IL)-4 and IL-13 and lower concentrations of IL-9, IL-17A and interferon-γ, compared with healthy breast-fed infants. At T0, there was a positive correlation between blood eosinophil numbers and plasma concentrations of IL-4, IL-9, IL-17A and IL-22. Treatment with a cows' milk elimination diet resulted in a decrease in plasma IL-4, IL-9, IL-13 and IL-22 and an increase in plasma IL-17A. We conclude that IL-4 and IL-13 are elevated in active CMA. The association of IL-9 and IL-22 with eosinophilia, and the decrease in these two cytokines with cows' milk elimination, suggests that they both play a role in the symptoms observed in CMA and may be important targets for future interventions.

Keywords: cows’ milk allergy; cytokine; dietetic treatment; free amino acid formula; hydrolysed soy formula.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Brazil
  • Eosinophilia / blood
  • Eosinophilia / diet therapy
  • Eosinophilia / immunology
  • Female
  • Humans
  • Infant
  • Infant Formula* / adverse effects
  • Interleukin-13 / blood
  • Interleukin-22
  • Interleukin-4 / blood
  • Interleukin-9 / blood*
  • Interleukins / blood*
  • Male
  • Milk Hypersensitivity / blood
  • Milk Hypersensitivity / diagnosis
  • Milk Hypersensitivity / diet therapy*
  • Milk Hypersensitivity / immunology
  • Prospective Studies
  • Protein Hydrolysates / administration & dosage*
  • Protein Hydrolysates / adverse effects
  • Soybean Proteins / administration & dosage*
  • Soybean Proteins / adverse effects
  • Time Factors
  • Treatment Outcome

Substances

  • IL4 protein, human
  • IL9 protein, human
  • Interleukin-13
  • Interleukin-9
  • Interleukins
  • Protein Hydrolysates
  • Soybean Proteins
  • Interleukin-4