Immunomodulatory Effect of Infectious Disease of a Breastfed Child on the Cellular Composition of Breast Milk.

Recent studies suggest that the content of immune components in milk is influenced by the mother's health and also by the infant she feeds. We aimed to evaluate the effect of a child's respiratory tract infection on the cellular composition of breast milk (neutrophils, monocytes, eosinophils, lymphocytes, and their subpopulations). Twenty-six breastfeeding mothers whose children were hospitalized for respiratory tract infections were enrolled in the study. The control group consisted of 23 mothers of healthy children. Regarding the children, baseline laboratory blood tests were performed, and nasal swabs were taken for the presence of RS virus. In the next step, milk samples were collected from the mothers to assess the cellular composition of the milk, including neutrophils, monocytes, eosinophils, lymphocytes, and their subpopulations. Significantly higher percentages of T lymphocytes (helper and cytotoxic lymphocytes) were observed in the milk of the studied mothers. There was a significantly higher percentage of milk lymphocytes in the group of affected children with confirmed RSV etiology than in children with excluded RSV etiology. A significant positive correlation was observed between the duration of infection and the percentage of milk NK cells and between milk CD19 lymphocytes and the child's serum leukocytosis. This study may provide evidence of a link between cells in breast milk and disease in the breastfed infant. The severity of the infection, its duration, and the etiological agent of the infection may affect the cellular composition of milk.

The Role of Vitamin D in COVID-19 and the Impact of Pandemic Restrictions on Vitamin D Blood Content.

Vitamin D is a hormone regulating the immune system and playing a pivotal role in responses to microbial infections. It regulates inflammatory processes by influencing the transcription of immune-response genes in macrophages, T cells, and dendritic cells. The proven role of vitamin D in many infectious diseases of the respiratory tract indicated that vitamin D should also play a role in SARS-CoV-2 infection. Vitamin D inhibits cytokine storm by switching the pro-inflammatory Th1 and Th17 to the anti-inflammatory Th2 and Treg response. Vitamin D is therefore expected to play a role in preventing, relieving symptoms, or treating SARS-CoV-2 infection symptoms, including severe pneumonia. There are several possible mechanisms by which vitamin D may reduce the risk of COVID-19 infection, such as induction of the transcription of cathelicidin and defensin. Also a nongenomic antiviral action of vitamin D and lumisterol, the molecule closely related to vitamin D, was reported. Despite this enormous progress, currently, there is still insufficient scientific evidence to support the claim that vitamin D supplementation may help treat COVID-19 infection. The pandemic restrictions were also shown to impact vitamin D uptake by limiting exposure to sunlight.

The Impact of COVID-19 Pandemic during 2020-2021 on the Vitamin D Serum Levels in the Paediatric Population in Warsaw, Poland.

BACKGROUND: The main source of vitamin D is skin synthesis, which depends on sunlight exposure. During the pandemic, COVID-19 children were obliged to home confinement, which potentially limiting sunlight exposure. The aim of this study was to evaluate whether home confinement led to decreased vitamin D serum levels in children in Warsaw, Poland. METHODS: The study included 1472 children who were divided into two groups, based on the date of 25(OH)D level blood sampling: before and during the pandemic. Children under 1 year of age (infants) were analysed separately. RESULTS: A statistically significant decrease in the average level of vitamin D was observed between groups of children over 1 year of age (35 ng/mL ± 18 vs. 31 ng/mL ± 14). In infants from both groups, the mean vitamin D levels were within the normal range (Group 1 inf 54 ng/mL ± 21 vs. Group 2 inf 47 ng/mL ± 15). The characteristic seasonal variability was observed before the pandemic, with maximal vitamin D levels in summer (40 ng/mL ± 17) and minimal levels in winter (30 ng/mL ± 14). During the pandemic, no seasonal variability was observed (summer 30 ng/mL ± 11 vs. winter 30 ng/mL ± 19). CONCLUSIONS: The COVID-19 pandemic restrictions led to a significant decrease in vitamin D serum levels in children.

Effects of Hyperbaric Oxygen Therapy in Children with Severe Atopic Dermatitis.

In the course of atopic dermatitis (AD), the overactivity of the immune system, associated with predominant Th2 lymphocyte responses, is observed, which leads to an increased inflammatory reaction. Cases of a severe course of atopic dermatitis lead to the search for new therapeutic options. The aim of this study was to assess the effects of hyperbaric oxygen therapy (HBOT) treatment for severe cases of AD in children. A total of 15 children with severe AD underwent therapy. The influence of HBOT on the clinical course of AD and immunomodulatory effect of the therapy was analyzed by the SCORAD and objective SCORAD (oSCORAD) scales and by determining the serum concentration of immunological parameters (blood: nTreg lymphocytes, CD4+CD25highCD127-FOXP3+, NKT lymphocytes CD3+, CD16/56+, and serum: total IgE, cytokines IL-4, IL-6, and IL-10, before and after the 30-day treatment cycle). The study showed a significant effect of the therapy on the improvement of the skin condition. In all children, a reduction in the extent and intensity of skin lesions, reduction of redness, swelling, oozing/crusting, scratch marks and skin lichenification after HBOT was observed. Patients also reported a reduction in the intensity of pruritus and an improvement in sleep quality after therapy. In all children, a statistically significant decrease in the serum level of IgE was observed. However, no statistically significant changes in the blood levels of IL-4, IL-6 and IL-10, as well as the percentage of CD4+CD25highCD127-FOXP3+ Treg and NKT lymphocytes, were found. In conclusion, the use of hyperbaric therapy has a positive impact on treatment results in children with a severe course of atopic dermatitis.

The Effect of Passive Exposure to Tobacco Smoke on the Immune Response in Children with Asthma.

Introduction: There are a few publications about the impact of tobacco smoke on the children's immune system. Material and Methods: The study group consisted of 43 children with asthma. The control group consisted of 37 healthy children. The exposure to tobacco smoke was assessed by the presence of the cotinine in the urine (metabolit of nicotine). Results: The group of children with asthma exposed to tobacco smoke had significantly higher levels of the IL-1 and lower levels IL-4 than children not exposed to the passive smoking. The children from the control group exposed to tobacco smoke had a significantly higher concentration of IL-4 than unexposed children. In the whole analyzed population, there was a significant positive correlation between cotinine-IL1 and cotinine-CRP. Conclusion: In this study we found that the passive exposure to tobacco smoke has the immunomodulatory effects on the immune system.

Vitamin D and Immunological Patterns of Allergic Diseases in Children.

Vitamin D, in addition to its superior role as a factor regulating calcium-phosphate metabolism, shows wide effects in other processes in the human body, including key functions of the immune system. This is due to the presence of vitamin D receptors in most cells of the human body. In our study, we aimed to assess whether there is a correlation between vitamin D content and the clinical course of allergic diseases as well as establish their immunological parameters in children. We found that vitamin D deficiency was significantly more frequent in the group of children with an allergic disease than in the control group (p = 0.007). Statistically significant higher vitamin D concentrations in blood were observed in the group of children with a mild course of the disease compared to children with a severe clinical course (p = 0.03). In the group of children with vitamin D deficiency, statistically significant lower percentages of NKT lymphocytes and T-regulatory lymphocytes were detected compared to the group of children without deficiency (respectively, p = 0.02 and p = 0.05), which highlights a potential weakness of the immune system in these patients. Furthermore, statistically higher levels of interleukin-22 were observed in the group of children with vitamin D deficiency (p = 0.01), suggesting a proinflammatory alert state. In conclusion, these results confirm the positive relationship between the optimal content of vitamin D and the lesser severity of allergic diseases in children, establishing weak points in the immune system caused by vitamin D deficiency in children.

Effects of vitamin D on macrophages and myeloid-derived suppressor cells (MDSCs) hyperinflammatory response in the lungs of COVID-19 patients.

Vitamin D regulates homeostasis, anti-microbial response, and inflammation. The vitamin D receptors are expressed in the macrophages and other immune cells, regulating the transcription of many different genes, including those coding the anti-microbial peptides. One of the most severe complications of the SARS-CoV-2 infection is the acute respiratory distress syndrome (ARDS) caused by the hyperinflammatory response (commonly called cytokine storm) of the lung macrophages. Studies showed that Vitamin D deficiency increases the severity of the ARDS in COVID-19 infection. We discuss here how the vitamin D supplementation may influence macrophage and myeloid-derived suppressor cells (MDSCs) inflammatory response, subdue the hyperinflammatory response, and lessen the ARDS in COVID-19 patients.

Excessive Body Weight and Immunological Response in Children with Allergic Diseases.

The prevalence of allergy and obesity is sharply on the rise in children. However, the nature of a mutual relation of the two conditions remains unclear. The aim of the study was to assess the impact of excessive body weight on the immune response in children with allergies. There were 56 children with allergies, aged 4-15 years, included into the study (41 with asthma and 15 with atopic dermatitis). Based on the body mass index, children were divided into two groups: normal weight (body mass index (BMI) <85th percentile) and excessive weight (BMI ≥ 85th percentile). The immunological parameters were evaluated by flow cytometry. We found that children with excessive body weight had a significantly lower percentage of CD4+ lymphocytes and a higher percentage of natural killer T cells (NKT) and CD16/56+ lymphocytes than those with normal weight. In the group with allergy, a significant positive association was noticed between BMI and the percentage of human leukocyte antigen (HLA)-DR-specific CD3. Further analysis was done after dividing the allergy group into the children with normal and excessive weight. There were an adverse association between BMI and the percentage of CD8+ lymphocytes in those with normal weight and a positive one between BMI and the percentage of CD4+ in those with excessive weight. We conclude that excessive body weight plays a major role in mediating the immunological response in children with allergy.

Influence of Vitamin D and Cotinine on T-Regulatory Cells and Asthma Severity in Children.

Asthma is a common chronic respiratory diseases in children. Understanding the immune mechanisms of epigenetic factors may contribute to a better control of asthma. This study seeks to determine the effects of serum vitamin D and urine cotinine on asthma severity and on T regulatory cells (Tregs) and other immune-related factors such as CD3, CD4, CD8, CD19, CD16/56, and anti-CD3 HLA-DR3. The study involved 34 children with asthma. Disease severity was assessed with the Asthma Control Test, spirometry, and the fractional exhaled nitric oxide (FeNO). The control group consisted of 18 healthy children. We found a significantly lower proportion of Tregs in the serum of asthmatic children compared with the control group (p < 0.002). There were no significant differences in the other immunological factors investigated. Nor was there any appreciable association between vitamin D or cotinine and the course of asthma, FeNO, Tregs, and the other immune factors. However, the percentage of Tregs was positively associated with the level of FeNO (p < 0.02). In conclusion, the study shows a role of T regulatory cells in the pathogenesis of asthma in children, but fails to show any influence of serum vitamin D or urine cotinine on disease course.

Evaluation of selected immunological parameters and the concentration of vitamin D in children with asthma. Case-control study.

Due to the increased incidence of allergic diseases and emerging effects of unsatisfactory control of asthma, new mechanisms for supervising the immune system should be searched. The aim of the study was to analyze the percentage of CD3, CD4, CD8, CD19, CD16/56, NKT, CD3 anti-HLADR3 and Foxp3 regulatory lymphocytes in patients with asthma. Additionally the correlation between immune parameters, severity of asthma and serum concentration of vitamin D was performed. 25 children diagnosed with asthma were enrolled. Disease severity was assessed with the Asthma Control Test (ACT) and spirometry. The control group consisted of 15 healthy children. Venous blood from each patient was collected on EDTA or on "clott". Phenotypes of lymphocytes were evaluated by flow cytometry. Vitamin D concentration was assessed by chemiluminescent immunoassay (CLIA) technology. There was a significant decrease in the percentage of T regulatory cells (p < 0.006) in children with asthma compared to the control group. There were no significant differences in the other investigated immunological parameters. In addition, in asthma group statistically significant decreased of vitamin D concentration (p < 0.04) was observed. There were also no significant correlations between vitamin D3 concentration and the course of asthma or percentage of regulatory cells. The results confirmed the role of regulatory T cells in the pathogenesis of asthma. Effects of vitamin D on the severity of the disease has not been proven.

Evaluation of Immune Indices and Serum Vitamin D Content in Children with Atopic Dermatitis.

The influence of vitamin D on allergic diseases, including atopic dermatitis, is linked to the presence of vitamin D nuclear receptors in immune cells. The present study seeks to determine the possible relationship between serum vitamin D content and immune indices in children with atopic dermatitis. The study was conducted in 19 children with atopic dermatitis. The control consisted of 17 age-matched healthy children. A single significant finding was a distinctly lower number of serum regulatory T cells in atopic dermatitis compared with controls (p < 0.00001). There were no appreciable differences between the two groups concerning the immunological indices such as the phenotypes: CD3, CD4, CD8, CD4/CD8, CD19, CD16/56, natural killer T cells, and anti-CD3 human leukocyte antigen - antigen D related cell surface receptor (HLA-DR3), or the percentage of lymphocytes, eosinophils, and the IgE level. We also revealed an inverse association between the serum vitamin D and the percentage of CD8+ cells (p < 0.05; r = 0.62) in atopic dermatitis. In conclusion, the results point to a regulatory role of T cells in the pathogenesis of atopic dermatitis, but fail to substantiate the influence of vitamin D on the course of the disease.