Atopic dermatitis in young children is associated with impaired interleukin-10 and interferon-γ responses to allergens, vaccines and colonizing skin and gut bacteria

BACKGROUND: A significant proportion of children with food allergy and more severe forms of atopic dermatis (AD) go on to develop persistent forms of allergic disease such asthma. Defining immune dysregulation in these children will be of great value in understanding disease pathogenesis. OBJECTIVE: In this study we characterized the immune responses of young infants (6-18 months of age) with moderate-to-severe AD (a modified SCORAD>or=25) and compared these (n=53) with responses of non-allergic children with no history of dermatitis or sensitization of the same age (n=20). METHODS: Mononuclear cell cytokine responses to allergens (egg ovalbumin (OVA), beta-lactoglobulin (BLG), house dust mite (HDM)), vaccines (tetanus toxoid (TT), diphtheria toxoid (DT)), intestinal flora (heat-killed Lactobacillus species (HKLB)), heat-killed Staphylococcus aureus (HKSA), S. aureus enterotoxin B (SEB) and mitogen (phytohaemaglutinin (PHA)) were compared in children with AD with unaffected children. RESULTS: Children with AD had significantly lower spontaneous (unstimulated) production of regulatory cytokine IL-10 (P<0.001), as well as IFN-gamma (P<0.001) and TNF-alpha (P<0.001) compared with the unaffected children. After allowing for differences in baseline levels IL-10 responses to virtually all stimuli (food allergens (P=0.003), vaccines P=0.01, intestinal flora (heat-killed Lactobacillus species (HKLB), P=0.005) and skin flora (heat-killed Staphylococcus aureus (HKSA), P=0.003)) were also significantly attenuated in children with AD. The only exception was HDM, to which responses were stronger in children with AD [P=0.05]. Although there were no significant correlations between HDM IgE and HDM cytokine responses at this age, T-helper type 2 (Th2) IL-5 (P=0.014) and IL-13 (P=0.004) responses to HDM were significantly more frequent in the children with AD. However, while children with AD showed significantly attenuated Th1 IFN-gamma responses to food allergens (OVA, P=0.007 and BLG, P<0.001) and vaccines (DT, P=0.008 and TT, P<0.001), these children showed no difference in Th1 IFN-gamma responses to HDM or microbial agents (HKSA and HKLB). CONCLUSION: A increase in propensity for Th2 responses to aeroallergens in children with AD is associated with early impaired production of IL-10 regulatory cytokine to a broad range of environmental stimuli including foods, intestinal flora, S. aureus, and vaccines.