Effects Of Vitamin A And Vitamin D On Peripheral Blood CD4⁺CD25⁺CD127^low Treg Cells And Cytokine IL-33 In Preschool Children With Recurrent Wheezing

Objective:To explore the effects of intervention of vitamin D and co-intervention of vitamin A and D who diagnosed with vitamin A deficiency on peripheral blood CD4+CD25+CD127low Treg cells and cytokines IL-33,IL-10,TGF-β1 and IL-17 in preschool children with recurrent wheezing.And to discuss the correlation between serum IL-33 level and peripheral blood CD4+CD25+CD127low Treg cells ratio,serum levels of IL-10,TGF-β1,IL-17 in preschool children with recurrent wheezing.Methods:Eighty preschool children with recurrent wheezing as well as 40 healthy preschool children were recruited in the study.63/80 wheezing children who volunteered to participate in and completed the follow-up were given basic antiinflammation and antiasthma treatment and divided into three groups:vitamin A and vitamin D co-intervention group(21 cases):children those who with vitamin A deficiency,was given vitamin AD(vitamin A 1500IU/day,vitamin D 500IU/day)orally for two consecutive months.Children those who without vitamin A deficiency were randomly divided into other two groups:the control group(20 cases)only given basic treatment;the vitamin D intervention group(22 cases)was given vitamin D(400 IU/day)orally for two consecutive months.Flow cytometry was used to detect the proportion of CD4+CD25+CD127low Treg cells in peripheral blood and enzyme-linked immunosorbent assay was used to detect serum levels of IL-33,IL-17,IL-10 and TGF-β1 in all children.The clinical effects of vitamin AD and vitamin D were observed respectively.Result:(1)Compared with the healthy group,the wheezing group has shown a significantly decrease in levels of serum vitamin A,25-(OH)D3,the ratio of peripheral blood CD4+CD25+CD127low Treg cells(P<0.01),and the levels of serum IL-10 and TGF-β1(P<0.05),while the levels of IL-33 and IL-17 increased apparently(P<0.05).(2)A negative correlation was found between the level of serum IL-33 and the ratio of peripheral blood CD4+CD25+CD127low Treg cells,the levels of serum IL-10 and TGF-β1 in preschool children with recurrent wheezing,but a positive correlation between the levels of serum IL-33 and IL-17(P<0.05).(3)A positive correlation existed among serum vitamin A、25-(OH)D3 and the ratio of peripheral blood CD4+CD25+CD127low Treg cells,the levels of serum IL-10 and TGF-β1 in preschool children with recurrent wheezing,but a negative correlation between the level of IL-17.Thereinto,there was a negative correlation between vitamin D and the level of IL-33(P<0.05).(4)We found a significantly increase in the percentage of peripheral blood CD4+CD25+CD127low Treg cells,the levels of serum IL-10 and TGF-β1 and decrease in the levels of serum IL-33 and IL-17 after treatment in peripheral blood of children with wheezing in the three groups(P<0.05).Compared with the control group,the percentage of peripheral blood CD4+CD25+CD127low Treg cells,the levels of serum IL-10 and TGF-β1 increased apparently,while the level of IL-17 decreased both in vitamin AD co-intervention group and vitamin D intervention group after excluding the effects of aerosol inhalation of glucocorticoids and minimal different doses of vitamin D,the difference was statistically significant(P<0.05).Compared with the group of vitamin D intervention,the percentage of peripheral blood CD4+CD25+CD127low Treg cells,the levels of serum IL-10 and TGF-β1 increased significantly,while the level of IL-17 decreased in the vitamin AD co-intervention group,the difference was statistically(P<0.05).Compared with the control group,the level of IL-33 in vitamin AD co-intervention group(P>0.05)and vitamin D intervention group was lower(P<0.05).While,compared with the vitamin D intervention group,the level of IL-33 was higher in vitamin AD co-intervention group(P>0.05).(5)There was no significant difference in the duration of wheezing,the druation of hospitalization and the times of wheezing recurrences among three groups(P>0.05).Conclusion:(1)It is more common and serious about vitamin A and/or D deficiency in preschool children with recurrent wheezing.(2)In preschool children with recurrent wheezing,CD4+CD25+CD127low Treg cells in peripheral blood and cytokines IL-33 and IL-17 may be involved in the inception and development of wheezing diseases,and there was a correlation between the level of serum IL-33 and the ratio of CD4+CD25+CD127low Treg cell in peripheral blood and the levels of serum IL-17,IL-10 and TGF-β1.We also found a correlation between the levels of serum vitamin A、D and the ratio of peripheral blood CD4+CD25+CD127low Treg cells,the levels of serum IL-33,IL-17,IL-10 and TGF-β1.(3)In preschool children with recurrent wheezing,vitamin D supplementation could promote the expression of CD4+CD25+CD127low Treg cells in peripheral blood and the secretion of cytokines IL-10 and TGF-Pi,and inhibit the secretion of cytokines IL-33 and IL-17,thus could promote the recovery of the disordered immune system.In preschool children with recurrent wheezing and vitamin A deficiency,adding of vitamin A on the basis of vitamin D supplementation could increase the expression of CD4+CD25+CD127low Treg cells in peripheral blood and the secretion of cytokines IL-10 and TGF-β1,but reduce the secretion of cytokine IL-17.And this will not cause immunologic derangement by taking vitamin A supplements in such a short term of 2-month-period.(4)Vitamin A and D supplementation in a 2-month-period did not significantly improve the clinical symptoms of preschool children with recurrent wheezing.