The Association between Vitamin D, Interleukin-4, and Interleukin-10 Levels and CD23+ Expression with Bronchial Asthma in Stunted Children

Abstract

Children with stunted growth have an increased risk of wheezing, and studies have shown that low levels of vitamin D and interleukin (IL)-10, along with increased IL-4 levels and CD23+ expression, are present in stunted and asthmatic children. To date, it is not known whether these factors are related to the incidence of asthma in stunted children. This case-control study investigated the association between vitamin D, IL-4, and IL-10 levels and CD23+ expression with bronchial asthma in stunted children. The study included 99 children aged 24-59 months, i.e., 37 stunted-sthmatic children (cases), 38 stunted children without asthma, and 24 non-stunted children with asthma. All children were tested for their 25(OH)D levels using chemiluminescent immunoassay (CLIA), IL-4 and IL-10 levels were measured through enzyme-linked immunosorbent assay (ELISA) testing, and CD23+ expression was measured through flow cytometry bead testing. The data were analyzed using chi-squared, Kruskal-Wallis, and Mann-Whitney tests. The results showed that stunted asthmatic children had a higher incidence of atopic family members than those without asthma. Additionally, stunted asthmatic children had a higher prevalence of vitamin D deficiency (48.6%) than the control group (44.7% and 20.8%). Furthermore, stunted asthmatic children had significantly lower levels of 25(OH)D [20.55 (16.18-25.55), p = 0.042] and higher levels of IL-4 [1.41 (0.95-2.40), p = 0.038], although there were no significant differences in IL-10 levels and CD23+ expression. The study concluded that low vitamin D and high IL-4 levels are associated with bronchial asthma in stunted children, while IL-10 and CD23+ do not show a significant association.

Keywords: 25(OH)D; CD23+; IL-10; IL-4; bronchial asthma; stunted.

Figure 1

Possible mechanism of asthma in stunted children. Stunted children have lower levels of vitamin D, which can lead to a decrease in linear growth. Low levels of vitamin D can also cause an imbalance in Th1–Th2 cells, which can lead to allergic diseases such as asthma. The development of asthma begins with exposure to allergens, which are captured by antigen presenting cells (APCs) and presented to naive CD4+ cells. With the help of IL-4, these cells become Th2 cells that produce IL-4 and IL-13. B lymphocytes then become plasma cells that produce IgE and attach to mast cells. Further exposure to allergens can trigger the release of histamine and lead to bronchoconstriction, causing wheezing and other asthma symptoms. When vitamin D levels are low, the number of Treg cells decreases, which can lead to an increase in Th2 activity and IL-4 production. This can result in an increase in IgE, which can further stabilize CD23+ B cells. B cells can then take up allergen–IgE complexes and present the allergen to Th2 cells, leading to an increase in the Th2 response. In stunted children, a decrease in lean body mass can cause impaired lung growth and decreased lung function. Low leptin levels can cause an imbalance in Th1–Th2 cells, leading to an increase in IL-4 production. In addition, it can cause an increase in Treg cells and IL-10, different from asthmatic children. B cells also increase, causing an increase in CD23+ levels. All of these factors can contribute to the development of asthma in stunted children. (red arrows: stunting paths, blue arrows: asthma paths).

Figure 2

Flow chart of the selection process for study participants.

Figure 3

Differences in 25(OH)D levels between stunted asthmatic children, stunted children without asthma, and non-stunted asthmatic children.

Figure 4

Differences in IL-4 levels between stunted asthmatic children, stunted children without asthma, and non-stunted asthmatic children.