Cow's Milk Allergy in Infants with Atopic Eczema is Associated with Aberrant Production of Interleukin‐4 During Oral Cow's Milk Challenge

Abstract

Objectives:A failure in the establishment and maintenance of oral tolerance in infancy may result in food allergy. To further assess the role of the intestinal immune system in cow's milk allergy (CMA), we investigated the systemic production of the pro‐allergenic Th2 cytokine interleukin (IL)‐4 and antiallergenic cytokines IL‐10, transforming growth factor (TGF)‐β1 and TGF‐β2 in infants suffering from atopic eczema with and without CMA during antigen elimination diet and oral antigen exposure.Methods:18 infants (mean age, 9.6 months; 95% confidence interval 8.1‐11.1 months) with atopic eczema and CMA and 17 infants (mean age, 9.7 months; 95% confidence interval 8.6‐10.9 months) with atopic eczema tolerant to milk as assessed by a double blind, placebo‐controlled cow's milk challenge were investigated. Peripheral blood mononuclear cells were obtained during antigen elimination diet and during oral cow's milk challenge and stimulated with Concanavalin‐A or cow's milk or were left unstimulated. The cytokine concentrations were measured by enzyme‐linked immunosorbent assay.Results:During antigen elimination, the Concanavalin A‐stimulated production of TGF‐β2 was significantly lower in infants with CMA as compared with infants without CMA: 129 pg/mL (interquartile ratio, 124‐144 pg/mL) vs. 149 pg/mL (interquartile ratio, 133‐169 pg/mL); P = 0.016. During oral antigen exposure, the immune responses in infants with CMA were characterized by significantly higher spontaneous production of IL‐4 as compared with those without CMA: 12.0 pg/mL (interquartile ratio, 5.2‐28.3 pg/mL) vs. 4.2 pg/mL (interquartile ratio, 1.5‐7.6 pg/mL); P = 0.018.Conclusions:Infants with atopic eczema and CMA exhibit markedly increased systemic pro‐allergenic IL‐4 responses on intestinal antigen contact, which may partially be explained by a defective ability to launch anti‐allergenic TGF‐β2 responses.