Cow’s milk protein allergy (CMPA) is the leading cause of food allergy in infants and young children younger than 3 years [1, 2], with diverse clinical presentation (e.g., cutaneous, gastrointestinal, and respiratory) of variable intensity in infants [1-3]. Although CMPA is thought to result from an immunological reaction to one or more milk proteins (e.g., immunoglobulin (Ig)E mediated, non-IgE mediated, or mixed) its aetiology is still unclear [1-3].
However, it is becoming evident that multiple factors, through modulation of immune response, can influence the development of CMPA . On this regard, numerous studies have examined the possible benefits of breast-feeding in comparison to cow’s milk formula-fed on food allergy in children [5, fig. 1].
Fig.1 Julia V, Macia L, Dombrowicz D. The impact of diet on asthma and allergic diseases. Nat Rev Immunol. 2015 May;15 (5):308-22
In fact, breast milk contains a multitude of immunologically active components, including interleukin (IL)-10, a major regulatory cytokine of inflammatory responses, which, by promoting the induction of Th-1 and the suppression of Th-2 function, helps infants in the essential immune adaptations [1, 3, fig. 2, 3].
Fig.2 Breastmilk composition (http://www.pregworld.org/breast-milk-composition/)
Fig.3 Kim AR, Kim HS, Kim do K, et al. Mesenteric IL-10-producing CD5+ regulatory B cells suppress cow's milk casein-induced allergic responses in mice. Sci Rep. 2016 Jan 20;6:19685.
IL-10, mainly produced by Th-reg, is a suppressive cytokine of T-cell proliferation in both Th1 and Th2 cells, and it seems to be an important immune factor to regulate the immune response, and it favors the immune tolerance . Herein, we evaluated if breast-feeding can represent a protective factor in CMPA-related atopic eczema/dermatitis syndrome (AEDS) children. Moreover, we measured serum IL-10 levels from breastfed and not breastfed infants with CMPA, during symptomatic and asymptomatic periods to evaluate its utility as marker of disease evolution.
Patients and Methods
32 breast-feeding children with CMPA-related AEDS (17 males and 15 females; mean age 5.56±2.41 months; 7 mild AD; 12 moderate AEDS; 13 severe AEDS) and 30 artificial feeding babies (16 males and 14 females; mean age 6.01±2.08 months; 14 mild AEDS; 5 moderate AEDS; 11 severe AEDS) were evaluated. 73 healthy children (39 males and 34 females; mean age was 5.51±2.93 months) were enrolled as control group.
The severity of AEDS was evaluated according to Score Atopic Dermatitis (SCORAD) index .
Subjects were eligible if they were affected by CMPA, assessed according to the NICE , positive cow’s milk challenge test and skin prick tests (SPT) or determination of serum total IgE levels.
Exclusion criteria were the following: associated diseases, any infection within one month before the start of the study, other skin diseases, positive SPT for additional food allergens, and use of any treatment, capable of interfering with the results in the previous month.
In all patients serum total IgE and IL-10 levels were detected.
Data were tabulated using Excel 2003 (Microsoft Corp., Redmond, WA, USA). The data collected were statistically analyzed by the statistical computer software SPSS, version 15.0. A p value of less than 0.05 was considered to be statistically significant.
We found significant Score Atopic Dermatitis (SCORAD) index point differences between breastfed and not breastfed children (p<0.001). The serum IL-10 levels were lower in children with CMPA as compared to the healthy control group (p<0.001). Moreover, we also detected a significant inverse correlation between serum IL-10 levels and SCORAD in both enrolled groups. In particular, IL-10 levels, in both groups, were significantly lower in children with severe symptoms. Conversely, serum IL-10 levels were significantly increased in children with mild-severe symptoms in both groups. Furthermore, breast-fed children, with lower severe symptoms, had higher serum IL-10 levels.
Finally, serum total IgE levels were negatively correlated with serum IL-10 levels in both breastfed and non-breastfed children with CMPA (p<0.001).
In the present study, we compared a group of breastfed patients with not-breastfed children in order to evaluate the role of breast-feeding on CMPA-related AEDS.
In our study, we have shown that breast-feeding is associated to a minor severity disease in CMPA-related AEDS children and it also promotes the systemic release of IL-10, reaching similar values to those found in control group.
These data are also in agreement with a recent observation that IL-10 has a central role in down-regulating inflammatory cascades [9, 10]. It is well established that IL-10 has also an important role in the regulation of Th2 and allergic responses. Our data confirmed this issue because artificial- feeding infants, with more severe symptoms, had lower IL-10 levels. Instead, breast-fed children, with lower severe symptoms, had higher serum IL-10 levels (4.66±0.38 pg/ml).
Our findings also confirm the hypothesis that AEDS severity, in subjects affected by CMPA, might be associated with an impaired regulation of IL-10. During follow-up, we observed a statistically significant increase of IL-10 serum levels in breastfed children that underwent a positive open oral challenge test. Our results suggest that breast-feeding, with the participation of suppressor cytokines, such as IL-10, may induce hyposensitization in children affected by CMPA. These findings indicate also that IL-10 may become a useful marker of disease improvement monitoring.
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