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

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.

Th9 cells in allergic diseases: A role for the microbiota?

“…43 Apart from the association with peanut allergy, a role for IL-9 secreting cells is also suggested in cow's milk allergy, since a study in cow's milk allergic children showed a correlation between IL-9 plasma levels and eosinophilia, which is known to contribute to allergy development. 44 Combined, these results stress the importance of Th9 cells in allergic pathologies and underline their potential as target for future allergy treatment, although further investigation is clearly needed.…”

“…Moreover, this study clearly characterized these IL‐9 secreting cells as Th9 cells and showed even a discriminatory Th9 response between peanut‐allergic and peanut‐sensitized children . Apart from the association with peanut allergy, a role for IL‐9 secreting cells is also suggested in cow's milk allergy, since a study in cow's milk allergic children showed a correlation between IL‐9 plasma levels and eosinophilia, which is known to contribute to allergy development …”

Cytokine profile in children with food allergy following liver transplantation

“…Increased levels of IL‐4 and IL‐13 and decreased levels of IL‐9, IL‐17A, and IFNy were recorded in children with cow's milk allergy compared with healthy controls. After 120 days of elimination diet, these patients had a decrease in IL‐4, IL‐9, IL‐13 and IL‐22, and an increase in IL‐17A …”

Association of T helper type 2 cytokines with sensitization to food in pediatric atopic dermatitis patients

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