Dynamics of background levels of serum cytokines in children with atopic dermatitis with concomitant pathology of oral mucosa in the course of optimized complex therapy
Authors: Slavinska Valentyna 
Published: June 2020

The purpose of the study was to study the dynamics of changes in the background level of serum IL-2, IL-4, IL-5, IL-10, IL-13, IFN-g and TNF-a in patients with various forms of AD with concomitant pathology of oral mucosa to find the optimal ways of using complex therapy.
Materials and methods. According to the design, 60 children (37 boys and 23 girls) with clinical manifestations of AD from 6 to 12 years of age participated in the study, who were on dispensary registration in the Department №6 of the Scientific and Diagnostic Center of Shevchenkivskyi district of Kyiv. No statistically significant differences were found between age groups. For the treatment of blood pressure, children with concomitant pathology of oral mucosa were prescribed the drug Montelukast. Children aged 6 to 12 years were advised to take a dose of 1 mg chewable tablet per night, in the evening. According to the study protocol Montelukast was taken 1 hour before or 2 hours after eating. In addition to Montelukast was proposed the use of Ketotifen. For children, Ketotifen was given at a dose of 1 mg 2 times daily, in the morning and in the evening, during meals for two weeks of systematic use. According to the study protocol for the treatment of blood pressure, children with concomitant pathology of oral mucosa were prescribed Spiramycin. The drug was prescribed pe os, children from 6 years – 1.5-3 million IU per 10 kg/day for 2-3 times, the duration of therapy was 10 days. Serum cytokine levels (IL-2, IL-4, IL-5, IL-10, IL-13, IFN-g and TNF-a) were determined by enzyme-linked immunosorbent assay (ELISA). To determine the concentration of cytokines used commercial kits of test systems of «IMMUNOTECH» and «DIACLONE», France.
Results. In patients with IgE-dependent AD after treatment there was a sharp increase in the concentration of IL-2 in the serum of peripheral blood 39.15 (30.5- 45.8)*, compared with the group of patients with IgE-independent AD 15.3 (10.6-29.9)* (p <0.001) and healthy donors 15.35 (10.1-14.3) (p<0.001).
In patients with IgE-dependent AD, a marked decrease in the IFN-g concentration of 3.2 (2.6-3.9)* was observed in patients with children compared with that in the IgE-independent AD group of patients 0.6 (0.1-1.6)* (p<0.001) and healthy donors 0.6 (0-4.3) (p<0.001) and TNF-a concentration ratio of 1.15 (0.3-1.8)* in comparison with similar rates in the group of sick children with IgE-independent form of AD 0.9 (0.5-1.4)* (p<0.01) and healthy donors 2.05 (1.6-3.1) (p<0.001).
And in patients with IgE-dependent AD with concomitant pathology of oral mucosa after treatment, there was a long-term increase in the concentration of IL-5 50.8 (45.7-65.7)* compared with the group of children with IgE-independent AD 22.25 (20.8-24.1)* (p<0.001) and control group 14.05 (11.5-16) (p<0.001). Serum IL-10 concentration levels were also significantly increased in patients with IgE-dependent AD 71.0 (61.7-89.5)* compared with those in children with IgE-independent AD 62.8 (59.6-67.1)* (p <0.011) and control group 45.25 (37.9-58,6) (p<0.001).
The level of IL-4 was slightly increased in the group of patients with IgE-dependent AD 32.9 (29.2-36.6)* and in the group with IgE-independent AD 26.2 (22.2-28.9)* (p<0.001) and control group 17.05 (15.3-19.3) (p<0.001). The serum IL-13 concentration level was also slightly increased in patients with IgE-dependent AD 24.6 (21.5-26.3)* compared with IgE-independent AD patients 22.75 (20.5-23.9)* (p< 0.013) and control group 12.6 (11.4-16.7) (p<0.001).
The study revealed sharp differences between serum IL-10 levels in patients with IgE-dependent and IgE-independent AD with concomitant pathology of oral mucosa after complex treatment. As it turned out, a sharp prolonged increase in IL-10 after treatment in serum was observed in all patients with IgE-dependent AD, in contrast to the level of this cytokine in groups of IgE-independent AD. This suggests that an imbalance in IL-10 level is not a leading pathogenetic factor in the development of an IgE-independent form of AD, unlike the IgE-dependent form, as previously reported.
As you know, IL-10 is a known biological marker of immunological tolerance. However, serum IL-10 levels are also capable of inducing both immunosuppressive processes and immunodeficiency states. This suggests that an increase in IL-10 synthesis under the conditions of high IL-2 detected shifts cytokine synthesis in patients with IgE-dependent AD in the direction of cytokine production by regulatory lymphocytes. In support of this conclusion, in patients with children with IgE-dependent form of AD with concomitant pathology of oral mucosa in our study revealed a prolonged increase in serum concentration of IL-10 after combination therapy, which coincides with a significant improvement in clinical status.
Conclusions

High levels of IL-2 and IL-10 detected in children with IgE-dependent atopic dermatitis with concomitant pathology of oral mucosa in our study confirm the important relationship between cytokine concentration and the stage of skin disease.
Continuous increase in the level of IL-10 subject to a decrease in the concentration of IL-4 in the blood of patients children on IgE-dependent form of BP with concomitant pathology of oral mucosa after the test combination therapy that coincides with the improvement of the clinical picture may serve as an important criterion for the formation of immunological tolerance.