Cytokines In Children Research Articles

Association between polymorphisms of IL4, IL13, IL10, STAT6 and IFNG genes, cytokines and immunoglobulin E levels with high burden of Schistosoma mansoni in children from schistosomiasis endemic areas of Cameroon.

Eliminating schistosomiasis as a public health problem by 2030 requires a better understanding of the disease transmission, especially the asymmetric distribution of worm burden in individuals living and sharing the same environment. It is in this light that this study was designed to identify human genetic determinants associated with high burden of S. mansoni and also with the plasma concentrations of IgE and four cytokines in children from two schistosomiasis endemic areas of Cameroon. In school-aged children of schistosomiasis endemic areas of Makenene and Nom-Kandi of Cameroon, S. mansoni infections and their infection intensities were evaluated in urine and stool samples using respectively the Point-of-care Circulating Cathodic Antigen test (POC-CCA) and the Kato Katz (KK) test. Thereafter, blood samples were collected in children harbouring high burden of schistosome infections as well as in their parents and siblings. DNA extracts and plasma were obtained from blood. Polymorphisms at 14 loci of five genes were assessed using PCR-restriction fragment length polymorphism and amplification-refractory mutation system. The ELISA test enabled to determine the plasma concentrations of IgE, IL-13, IL-10, IL-4 and IFN-γ. The prevalence of S. mansoni infections was significantly higher (P<0.0001 for POC-CCA; P=0.001 for KK) in Makenene (48.6% for POC-CCA and 7.9% for KK) compared to Nom-Kandi (31% for POC-CCA and 4.3% for KK). The infection intensities were also higher (P<0.0001 for POC-CCA; P=0.001 for KK) in children from Makenene than those from Nom-Kandi. The allele C of SNP rs3024974 of STAT6 was associated with an increased risk of bearing high burden of S. mansoni both in the additive (p=0.009) and recessive model (p=0.01) while the allele C of SNP rs1800871 of IL10 was protective (p=0.0009) against high burden of S. mansoni. The alleles A of SNP rs2069739 of IL13 and G of SNP rs2243283 of IL4 were associated with an increased risk of having low plasma concentrations of IL-13 (P=0.04) and IL-10 (P=0.04), respectively. This study showed that host genetic polymorphisms may influence the outcome (high or low worm burden) of S. mansoni infections and also the plasma concentrations of some cytokines.

Impact of vitamin D in children with chronic tonsillitis (immunohistochemical study of CD68 polarisation and proinflammatory cytokines estimation)

Inflammatory processes are increasingly attributed to macrophage polarization. Proinflammatory macrophages promote T helper (Th) 1 response, tissue repair, and Th2 responses. Detection of macrophages in tissue sections is facilitated by CD68. Our study is focused on the expression of CD68 and the estimation of proinflammatory cytokines in children’s patients with chronic tonsillitis secondary to vitamin D supplementation. This hospital-based Randomized prospective case–control study was conducted on 80 children with chronic tonsillitis associated with vitamin D deficiency where (40 received vitamin D 50,000 IU weekly for 3–6 months and 40 received 5 ml distilled water as placebo). The serum 25-hydroxyvitamin D [25(OH)D] was measured using an Enzyme-linked immunosorbent assay on all included children. Different histological and immunohistochemical studies for the detection of CD68 were done. There was a significantly lower serum level of 25(OH)D in the placebo group versus the vitamin D group (P < 0.001). The levels of pro-inflammatory cytokines, TNFα, and IL-2 significantly increased in the placebo group as compared to the vitamin D group (P < 0.001). The increased level of IL-4 and IL-10 in the placebo group as compared to the vitamin D group was insignificant (P = 0.32, 0.82) respectively. Vitamin D supplementation alleviated the deleterious effect of chronic tonsillitis on the histological structure of the tonsil. Tonsillar tissues of the children in the control and vitamin D groups demonstrated a highly statistically significantly lower number of CD68 immunoexpressing cells compared with those in the placebo group (P < 0.001). Low vitamin D may play a role in chronic tonsillitis. Vitamin D supplementation could help reduce the occurrence of chronic tonsillitis in susceptible children.

Preliminary Findings of Elevated Inflammatory Plasma Cytokines in Children with Autism Who Have Co-Morbid Gastrointestinal Symptoms.

Autism spectrum disorder (AU) is present in approximately 2% of the population and is often associated with co-morbidities that can impact quality of life. One of the most common co-morbidities in autism is the presence of gastrointestinal (GI) symptoms consisting of irregular bowel habits such as constipation, diarrhea, or alternating bowel habit. Evidence of immune infiltration and immune activation has been shown in the ileum and colon of children with AU with GI symptoms. Moreover, immune dysfunction is a contributing factor in many GI diseases, and we hypothesize that it would be more apparent in children with AU that exhibit GI symptoms than those who do not present with GI symptoms. The aim of this preliminary study was to determine whether there are altered cytokine levels in plasma in children with AU with GI symptoms compared with children with AU without GI symptoms, typically developing (TD) children with GI symptoms and TD children without GI symptoms, from the same population-based cohort. Plasma cytokine levels were assessed by multiplex assays. No differences in plasma cytokines were observed in TD controls with or without GI symptoms; however, many innate (IL-1α, TNFα, GM-CSF, IFNα) and adaptive cytokines (IL-4, IL-13, IL-12p70) were increased in AU children with GI symptoms compared with children with AU with no GI symptoms. The mucosal relevant cytokine IL-15 was increased in AU with GI symptoms compared with all groups. In contrast, the regulatory cytokine IL-10, was reduced in AU with GI symptoms and may suggest an imbalance in pro-inflammatory/regulatory signals. These data suggest that children with AU and GI symptoms have an imbalance in their immune response that is evident in their circulating plasma cytokine levels. A finding that could point to potential therapeutic and/or monitoring strategies for GI issues in AU.

The role of IL-33 and IL-1β in the development of persistent allergic rhinitis in overweight/obese children

BACKGROUND: Few works were devoted to the study of the role of cytokines in children with allergic rhinitis (AR) with comorbid obesity.&#x0D; AIMS: To study the level of cytokines interleukin (IL)1, IL-33, IL-6, tumor necrosis factor (TNF)-, and total IgE in the blood serum of overweight/obese children with intermittent and persistent AR.&#x0D; MATERIALS AND METHODS: This cross-sectional observational study analyzed 69 children aged 710 years with AR in the remission period and was conducted from November 2020 to February 2021. All children went through a comprehensive examination for 3 days, including the definition of the serum concentrations IL-1, IL-33, IL-6, TNF-, and total IgE. Before blood sampling, children did not use nasal glucocorticosteroids, antileukotriene drugs for the last 4 weeks, and antihistamines for the last 7 days. Bioimpedansometry was used to assess the body weight by calculating the %FM (percentage of body fat mass).&#x0D; RESULTS: The study included 44 children with AR and overweight/obesity (group I) and 25 children with AR and normal body weight (group II). The analysis of AR showed that in group I, intermittent AR was detected in 11 (25.0%) children (subgroup IA), whereas a persistent course was found in 33 children (75.0%) (subgroup IB). In group II, intermittent AR was detected in 13 (52.0%) children (subgroup IIA), whereas persistent AR in 12 children (48.0%) (subgroup IIB). The level of IL-1 in the blood serum was significantly higher in the subgroup IB than in subgroup IA (p=0.009). The concentration of IL-33 in children with persistent AR and obesity was significantly lower than that in children with intermittent AR and obesity (p=0.039). The level of IL-33 in the serum negatively correlated with %FM in group IA (r=-0.6673, p=0.035). The concentration of IL-1 negatively correlated with %FM in group IIB (r=-0,738, p=0,037). The levels of IL-6, TNF, and total IgE in obese children did not depend on the severity of AR.&#x0D; CONCLUSIONS: The predictors of persistent AR in children with obesity are a decrease in the level of IL-33 and an increase in IL-1 in the blood serum. The negative correlation between the degree of obesity and IL-33 concentration in children with intermittent AR opens a window of opportunity for the personified management of children with AR and comorbid obesity.

Analysis of selected pro-inflammatory cytokines: IL-1β, IL-6, CXCL-8, and TNF-α in children with seizure disorders during acute infection. Is there a specific pro-inflammatory cytokine profile in these patients?

Introduction and objective: This study aimed to analyse the levels of selected pro-inflammatory cytokines in children with seizures during acute infection. Materials and methods: The study was conducted in the Department of Infectious Diseases and Child Neurology of the Poznan University of Medical Sciences from 19 January 2017 to 5 December 2020. Pro-inflammatory cytokines were measured in 64 patients with febrile seizures and 11 patients after an epileptic seizure in generalised epilepsy. The control group comprised 46 patients with delayed development. Serum pro-inflammatory cytokines were determined using the BioLegend’s ELISA MAX™ Deluxe Set. Pathogens were detected by standard diagnostic methods. Total white blood cell count, C-reactive protein and procalcitonin were determined using standard diagnostic methods. Results: Significantly higher levels of all analysed pro-inflammatory cytokines were found in patients with simple and simple plus febrile seizures; interleukin 6, CXCL-8 in those with complex febrile seizures; interleukin 6, CXCL-8, tumour necrosis factor α following epileptic seizure. The intensity of the inflammatory response in simple and simple plus febrile seizure patients corresponded to significantly higher levels of all pro-inflammatory cytokines and inflammatory markers. Pro-inflammatory profiles differed depending on the aetiology of the infection. Significantly higher levels interleukin 6, CXCL-8, tumour necrosis factor α were found in simple and simple plus febrile seizure patients infected with human herpesvirus-6 compared to the control group. Conclusions: In patients with febrile seizures and epileptic seizures, the involvement of interleukin 1β, interleukin 6, CXCL-8, and tumour necrosis factor α was confirmed in the inflammatory process, with a different distribution in the analysed groups. Pro-inflammatory cytokine profiles varied depending on the infectious aetiology.

Correlation analysis between cytokines' profile, autoimmune antibodies and the duration of type 1 diabetes: A case control study in a specialized children's centre in Riyadh.

The aim of this study was to investigate the role of cytokines in children with T1D living in Saudi Arabia and their correlation with disease duration and autoimmune antibody markers. A case-control study was conducted in the endocrine clinic of King Abdullah Specialized Children's Hospital in Riyadh. A total of 274 T1D and healthy control children were enrolled in the study. 5mL of venous blood samples were collected in the morning after 9 to 12h of fasting in BD Vacutainer® EDTA tubes and centrifuged at 250g for 15min at. Plasma was then stored at -20°C for detection of anti-islet, anti-GAD antibodies (Abs), and C-peptide using commercial ELISA kits from Thermo Fisher Scientific. The levels of cytokines were measured using commercial sandwich ELISA kits from Abcam. Median differences in cytokine levels (IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-13, IL-18, IL-21, IL-35, and IL-37) were significantly higher in T1D patients compared with healthy controls (p-value < .001). Spearman's Rho correlation indicated that TNFα, IL-1β, IL-4, IL-10, IL-13, and IL-21 correlated significantly with T1D Abs (p-value = .01). HbA1C correlated negatively with IL-35 and IL-37, and positively with IL-18 (p-value = .01). Linear regression analysis showed a significant increase in anti-glutamic acid antibodies (GAD) in patients with >3years of T1D duration. Autoantibodies remained positive at high levels in our patients over a 3-year duration of the disease and correlated with specific cytokines. The clear correlations with disease duration and profile of specific cytokines could be targets for future therapeutic interventions.

2160. Mucosal Antiviral Cytokine Responses Are Impaired in Children and Adolescents with Severe COVID-19

Abstract Background The factors associated with severe COVID-19 in pediatric patients remain poorly understood. We sought to determine whether mucosal innate immunity cytokines were associated with disease severity in children and adolescents with acute COVID-19. Methods Single-center, prospective study including children and adolescents &amp;lt; 21 years of age hospitalized because of symptomatic COVID-19 from 3/2020 to 1/2021, and age, sex and race matched pre-pandemic (2016-2019) healthy controls. Nasopharyngeal (NP) samples were obtained at enrollment for measurement of SARS-CoV-2 viral loads by rt-PCR and cytokine concentrations using a 92-plex inflammation/antiviral panel (Olink). Disease severity was assessed by the need for supplemental oxygen or PICU admission, and patients classified as severe and non-severe based on these two parameters. Statistical analyses were performed in R studio and Benjamini-Hochberg applied to adjust for multiple comparisons. Results Of the 75 children with acute COVID-19 (median IQR age: 3.4 [0.2-15.3] years), 28 (37%) were classified as severe COVID-19 (19 PICU; 25 supplemental oxygen) and 47 (63%) were non-severe. Children with severe COVID-19 were predominantly male and had an underlying condition more frequently than those with non-severe disease (79% vs 49% respectively; p&amp;lt; 0.01, Table 1). SARS-CoV-2 viral loads were comparable between groups, yet patients with severe COVID-19 had significantly higher concentrations of C-reactive protein (p=0.04), more frequent lymphopenia (p=0.03) and cardiac involvement (p=0.04), and received COVID-19 directed therapies more commonly (p&amp;lt; 0.001). Comparative analyses identified 24 cytokines that were significantly different between children with acute COVID-19 versus 45 healthy controls. Of those, concentrations of IFN-γ (p=0.004), CXCL10 (p=0.01), CXCL11 (p=0.02) and CCL19 (p=0.02) were significantly lower in children with severe versus those with non-severe COVID-19 (Fig 1). Table 1.Demographic and clinical characteristics in children with symptomatic COVID-19*Bolded p-values indicates statistical significance. Abbreviations: N, number. CRP, C-Reactive protein; PICU, pediatric intensive care unit.**Other including the following underlying conditions: prematurity, endocrine conditions, immunocompromising conditions, prematurity, trisomy 21 and complex care. Ł Lymphopenia defined as an ALC of &amp;lt;4,500 cells/μl in infants, and &amp;lt;1,500 cells /μl in children &amp;gt;12 months of age Continuous variables displayed as medians and 25%-75% interquartile ranges (IQR), Mann-Whitney test was used to determine differences between two groups; Kruskal-Wallis &amp; Dunn’s multiple test correction was used to determine differences between three groups (p-values*). Categorical data expressed as numbers and proportions (in parenthesis) and analyzed by Fisher’s exact test or Chi square test. Figure 1.Nasal mucosal concentrations of antiviral/regulatory cytokines in children with symptomatic COVID-19 according to disease severity Conclusion Mucosal concentrations of antiviral/regulatory cytokines were decreased in children with severe COVID-19. These findings suggest that impaired mucosal innate immune responses might favor SARS-CoV-2 disease progression and severity in children. Disclosures Amy Leber, PhD, BioFire: Advisor/Consultant|BioFire: Grant/Research Support|Biorad: Advisor/Consultant|Cepheid: Grant/Research Support Octavio Ramilo, MD, Adagio: Advisor/Consultant|Bill &amp; Melinda Gates Foundation: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Lilly: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|NIH: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Sanofi: Advisor/Consultant|Sanofi: Honoraria Asuncion Mejias, MD, PhD, MsCS, AstraZeneca: Honoraria|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Roche: Advisor/Consultant|Sanofi-Pasteur: Advisor/Consultant|Sanofi-Pasteur: Honoraria.

Profiles and predictive value of cytokines in children with human metapneumovirus pneumonia.

Human metapneumovirus (HMPV) is an important cause of respiratory tract infections in young children. Early innate immune response to HMPV is focused on induction of antiviral interferons (IFNs) and other pro-inflammatory cytokines that are critical for the formation of adaptive immune responses. To evaluate the predictive value of Th1/Th2 cytokines which include IL-2, IL-4, IL-6, IL-10, INF-γ and TNF-α in pneumonia caused by HMPV. A retrospective study was performed among 59 pneumonia pediatric patients with HMPV infection and 33 healthy children as the control cohort, which was detected by the immunofluorescence assay, and the Th1/Th2 cytokines were measured by flow cytometry. 131 children infected with Influenza virus A (IVA) and 41 children infected with influenza virus B (IVB) were detected by RT-PCR assay in throat swabs. When compared with the healthy children, children who were infected with HMPV pneumonia had a significantly lower level of IL-2 (p < 0.001) and higher levels of IL-4 (p < 0.001), IL-6 (p = 0.001), IL-10 (p < 0.001), and IFN-γ (p < 0.001). Compared with patients diagnosed with IVA or IVB infection, HMPV-positive patients had significantly higher levels of IL-4 (p < 0.001 and < 0.001), IFN-γ (p < 0.001 and < 0.001), and TNF-α (p < 0.001 and 0.016). Moreover, compared with IVA patients, HMPV-positive patients had a significantly lower level of IL-6 (p = 0.033). Finally, when comparing cytokine levels among the patients with HMPV pneumonia, IL-6 and TNF-α levels were found to be significantly higher in the severe group than the mild group (p = 0.027 and 0.049). The IL-6 and TNF-α were used to differentiate between mild symptoms and severe symptoms in children diagnosed with HMPV pneumonia with an AUC of 0.678 (95% CI 0.526-0.829) and 0.658 (95% CI 0.506-0.809), respectively. Our study indicated that difference in cytokine trends depending on the virus species. The levels of IL-4, TNF-α and IFN-γ were significantly distinguished in children infected with HMPV versus IVA and IVB. IL-6 and TNF-α may be helpful in assessing the severity and prognosis of HMPV infection.

Serum dual-specificity phosphatase 1 reflects decreased exacerbation risk, correlates with less advanced exacerbation severity and lower inflammatory cytokines in children with asthma.

It is as fact that dual-specificity phosphatase 1 (DUSP1) regulates the T cell activation, pro-allergic response, and inflammation to engage with the pathogenesis of asthma, but its clinical role in children with asthma is unclear. The present study aimed to explore the expression of DUSP1, its association with exacerbation risk, severity, and inflammatory cytokines in children with asthma. Around 52 children with asthma-exacerbation, 50 children in asthma-remission, and 50 healthy children were chosen for the study. The serum levels of DUSP1, as well as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-17 were detected by the enzyme-linked immunosorbent assay. The levels of DUSP1 was the highest in healthy children (median (IQR)=34.305 (25.892- 43.693) ng/mL), the second highest in children in asthma-remission (median (IQR)=21.471 (18.581-27.934) ng/mL), and the lowest in children with asthma-exacerbation (median (IQR)=13.982 (7.901-21.624) ng/mL) (P<0.001). At the same time, DUSP1 was also related to decreased asthma risk with area under curve (AUC) (95%CI) of 0.847 (0.780-0.914), and correlated with its lower exacerbation risk with AUC (95%CI) of 0.755 (0.661-0.849). Besides, DUSP1 was negatively linked with exacerbation severity (rs =-0.338, P=0.014), immunoglobulin E (rs =-0.277, P=0.047), TNF-α (rs =-0.423, P=0.002), IL-1β (rs =-0.389, P=0.004), and IL-17 (rs =-0.293, P=0.035), but not related with other disease features in children with asthma-exacerbation. Meanwhile, DUSP1 was only negatively associated with TNF-α (rs=-0.300, P=0.034) and IL-1β (rs =-0.309, P=0.029) in children in asthma-remission. However, no correlation was found in DUSP1 with inflammatory cytokines or other disease features in healthy children (all P>0.05). DUSP1 reflects the reduced exacerbation risk, and associates with lower exacerbation severity and inflammatory cytokines in children with asthma-exacerbation; it also associates with inflammatory cytokines in children in asthma-remission. These findings suggest that DUSP1 may help to improve the management of asthmatic children.

Plasma human growth cytokines in children with vasovagal syncope.

PurposeThe study was designed to investigate the profile of plasma human growth cytokines in pediatric vasovagal syncope (VVS).Materials and methodsIn the discovery set of the study, plasma human growth cytokines were measured using a Quantiboby Human Growth Factor Array in 24 VVS children and 12 healthy controls. Scatter and principal component analysis (PCA) diagrams were used to describe the samples, an unsupervised hierarchical clustering analysis was used to categorize the samples. Subsequently, the cytokines obtained from the screening assays were verified with a suspension cytokine array in the validation set of the study including 53 VVS children and 24 controls. Finally, the factors associated with pediatric VVS and the predictive value for the diagnosis of VVS were determined.ResultsIn the discovery study, the differential protein screening revealed that the plasma hepatocyte growth factor (HGF), transforming growth factor b1 (TGF-b1), insulin-like growth factor binding protein (IGFBP)-4, and IGFBP-1 in children suffering from VVS were higher than those of the controls (all adjust P- value < 0.05). However, the plasma IGFBP-6, epidermal growth factor (EGF), and IGFBP-3 in pediatric VVS were lower than those of the controls (all adjust P- value < 0.01). Meanwhile, the changes of 7 differential proteins were analyzed by volcano plot. Unsupervised hierarchical cluster analysis demonstrated that patients in the VVS group could be successfully distinguished from controls based on the plasma level of seven differential proteins. Further validation experiments showed that VVS patients had significantly higher plasma concentrations of HGF, IGFBP-1, and IGFBP-6, but lower plasma concentrations of EGF and IGFBP-3 than controls. The logistics regression model showed that increased plasma concentration of HGF and IGFBP-1 and decreased plasma concentration of EGF were correlated with the development of pediatric VVS. ROC curve analysis showed that the abovementioned 3 proteins were useful for assisting the diagnosis of VVS.ConclusionPlasma human growth cytokine profiling changed in pediatric VVS. Elevated plasma concentrations of HGF and IGFBP-1, and decreased EGF were associated factors in the development of pediatric VVS. The abovementioned three proteins are helpful for the diagnosis of pediatric VVS.

Blood levels of pro- and anti-inflammatory cytokines in children after acute kidney injury at different stages of observation

Identifying the factors for progression of kidney pathology after acute kidney injury (AKI) in children is important for making clinical decisions and creating strategies for the prevention and treatment of chronic kidney disease (CKD).&#x0D; The present study aimed to investigate the value of serum levels of tumor necrosis factor α (TNF-α) and transforming growth factor (TGF-β) as markers of CKD progression in children after AKI.&#x0D; Methods. In this cross-sectional cohort study, the levels of serum cytokines were studied in 63 children from 6 months to 18 years old who had undergone AKI and 10 healthy children (reference group) using ELISA. The peculiarities of those who recovered (n=14) and those who were subsequently diagnosed with CKD stage 1 ​ (n=22) or CKD stages 2-3 (n=27) were determined. An analysis was also carried out taking into account the duration from the episode of AKI: early recovery period up to 3 months (n=21), 3-12 months (n=9), 1-3 years (n=22), and more than 3 years (n=11). “SPSS for Windows. Version 11" - Student's test or Mann-Whitney Rank Sum Test was used. The correlation analysis was determined using the Pearson (r) or Kendall/Spearman method (ρ).&#x0D; Results. An increase in serum levels of the anti-inflammatory but pro-sclerotic TGF-β was observed in all children convalescing with AKI regardless of disease progression, with mean levels of the indicator increasing in the delayed phase. An increase in TGF-β levels ≥40.5 pg/mL in the first 3 months after AKI was documented in patients with an unfavorable disease course, such that these patients could be classified as a risk group for the development of fibrotic complications.&#x0D; No peculiarities in mean serum levels of proinflammatory TNF-α were observed in children who had suffered AKI, and there was no significant difference when comparing the groups according to the consequences of the disease. In the individual analysis, it was found that after the 12th month of observation, a high TNF-α level (≥8.0 pg/ml) was associated with an increase in the proportion of patients with CKD 2-3 (p &lt; 0.001), which can be used to predict disease progression.&#x0D; Conclusions. This study demonstrates the feasibility of determining serum levels of TNF-α and TGF-β in children with AKI, which could be used as potential predictors of CKD risk to optimize treatment and prevention.

Effect of Vitamin D Supplementation on Inflammatory Biomarkers in School-Aged Children with Attention Deficit Hyperactivity Disorder.

Method This randomized double-blind, placebo-controlled trial was conducted on 75 school-aged children with a diagnosis of ADHD based on DSM-V criteria. Children were randomly allocated to receive either vitamin D3 (2000 IU/day) or a placebo for 3 months. Serum IL-6, TNF-α, and 25(OH) D were assessed before and after the intervention to determine the effects of vitamin D on the highlighted parameters. Results Serum levels of 25(OH) D increased significantly in the vitamin D group (P=0.01). However, no significant differences in serum IL-6 and TNF-α were found between both groups at the baseline and at the end of the intervention. Conclusion The findings revealed that vitamin D supplementation for 3 months is not efficacious in reducing inflammatory cytokines in children with ADHD. Further studies are required to confirm these results.

Value of autotaxin in predicting refractory Mycoplasma pneumoniae pneumonia in children and its correlation with inflammatory cytokines

To study the value of autotaxin (an autocrine motility factor) level in serum and bronchoalveolar lavage fluid (BALF) in predicting refractory Mycoplasma pneumoniae pneumonia (RMPP) in children and its correlation with interleukin-6 (IL-6), interleukin-8 (IL-8), and C-reactive protein (CRP). A retrospective analysis was performed on 238 children with Mycoplasma pneumoniae pneumonia who were admitted from January 2019 to December 2021. According to disease severity, they were divided into two groups: RMPP (n=82) and general Mycoplasma pneumoniae pneumonia (GMPP; n=156). The two groups were compared in terms of the levels of autotaxin, IL-6, IL-8, and CRP in serum and BALF to study the value of autotaxin level in serum and BALF in predicting RMPP in children, as well as the correlation of autotaxin level with IL-6, IL-8, and CRP in children with RMPP. Compared with the GMPP group, the RMPP group had significantly higher levels of autotaxin, IL-6, IL-8, and CRP in serum and BALF (P<0.05). For the children with RMPP, the levels of autotaxin, IL-6, IL-8, and CRP in serum and BALF in the acute stage were significantly higher than those in the convalescent stage (P<0.05). The receiver operating characteristic (ROC) curve showed that the level of autotaxin in serum and BALF had a good value in predicting RMPP in children, with an area under the curve of 0.874 (95%CI: 0.816-0.935) and 0.862 (95%CI: 0.802-0.924), respectively. The correlation analysis showed that the level of autotaxin in serum and BALF was positively correlated with IL-6, IL-8, and CRP levels (P<0.001). The level of autotaxin in serum and BALF increases and is correlated with the degree of disease recovery and inflammatory cytokines in children with RMPP. Autotaxin can be used as a predictive indicator for RMPP in children.

Increased Systemic Inflammatory Response with Mast Cell Activation In Elder Children With Cerebral Palsy

Objective: Increased systemic inflammatory response during intrauterine period or period before the age of 3 is associated with cerebral palsy (CP) pathogenesis; however, effects of inflammatory processes involving mast cell activation in elder children with CP remain unclear. We aimed to investigate the role of mast cells and proinflammatory cytokines in children with CP at 3-18 years of age.&#x0D; Methods: In this cross-sectional study, venous blood samples were obtained from 30 volunteers with CP and 26 healthy volunteers at 3-18 years of age. Plasma levels of proinflammatory cytokines (IL-1β, IL-6 and IL-9) and mast cell biomarkers (histamine and tryptase beta-2) were determined using ELISA.&#x0D; Results: IL-1β, IL-6 and histamine levels were higher in individuals with CP compared to healthy controls. Likewise, IL-1β, IL-6, IL-9 and histamine levels were higher in the female patients with CP compared to the male patients, and in the female patients in adolescence compared to the female patients in pre-adolescence.&#x0D; Conclusion: Our findings indicate that the increased inflammatory response contributes to the pathogenesis of the disease in children with CP who are older than 2 years of age. Moreover the increased inflammatory response is more effective in female patients than in male patients, suggesting that there may be a gender difference in CP. Additionally mast cell activation contributes to the exacerbation of systemic inflammatory response in children with CP at 3-18 years of age.

Some Pro and Anti-Inflammatory Cytokines in Children with Tonsillitis and their Correlations with Vitamin D Deficiency

Inflammation of the tonsils could be described as acute tonsillitis, mainly due to infection. Recurrent tonsillitis could be defined as 3-7 episodes during the first 3 years of age. Vitamin D, which is a neuro-hormone with pleiotropic biological activities may modulate the immune response by alleviation, and stimulation of Th1 and Th2 cell proliferation, respectively, that influence the stimulation, synthesis, and secretion of both pro and anti-inflammatory cytokines. In this study we aimed to shed light on the levels of vitamin D in children with different episodes of tonsillitis in association with levels of interleukins (TNFα, IL-2, IL-4, IL-10). Blood samples were collected from 48 participants in 3 groups: control, acute tonsillitis (1-2 episodes/year), chronic tonsillitis (more than 7 episodes/year), serum was separated and the levels of Vitamin D, TNFα, IL-2, IL-4 and IL-10 were estimated using ELISA technique. Vitamin D decreased significantly as the episodes of tonsillitis increased, with level of 16.38± 2.41ng/ml in acute and, 14.13± 2.15 ng/ml in chronic tonsillitis as compared to control (30.91± 2.31 ng/ml), while pro-inflammatory cytokines (TNFα and IL-2) significantly increased (46.88± 14.05 and 44.55± 9.24, 1267.25± 111.85 and 1191.72± 121.52 ng/ml, respectively) as compared to control (9.45 and 138.48 ng/ml respectively). Anti-inflammatory (IL-4, IL-10) cytokines in control group were (243.08± 28.72 and 24.27± 1.83 ng/ml, respectively), which increased non-significantly in acute and chronic tonsillitis (302.76± 38.93, 290.12± 44.69 and 28.16± 2.01, 26.29± 1.99 ng/ml, respectively). Significant direct correlation was observed between the levels of vitamin D and anti-inflammatory cytokines in chronic tonsillitis (P&lt;0.05). In conclusion, deficiency of vitamin D may affect the number of episodes of tonsillitis in children by modulation of the secretion of some cytokines.

Evaluation of periodontal parameters and gingival crevicular fluid cytokines in children with anterior open bite receiving passive orthodontic treatment with a spur.

ObjectiveTo evaluate clinical parameters and gingival crevicular fluid (GCF) cytokines in children with anterior open bite receiving passive orthodontic treatment with spurs.MethodsTwenty children with indications for interceptive orthodontic treatment, an anterior open bite, and good oral hygiene and periodontal health were included in this study. GCF samples were collected from the mandibular and maxillary central incisors before (baseline) and 24 hours and 7 days after spur bonding. Clinical and periodontal examinations and cytokine analyses were performed.ResultsAt 7 days after spur attachment, gingival bleeding in the mandibular group was increased relative to that in the maxillary group. Visible plaque was correlated with gingival bleeding at 7 days and the GCF volume at 24 hours after spur attachment. Compared with those at baseline, interleukin (IL)-8 levels in the maxillary group and IL-1β levels in both tooth groups increased at both 24 hours and 7 days and at 7 days, respectively. At 24 hours, IL-8, IL-1β, and IL-6 levels were higher in the maxillary group than in the mandibular group. Cytokine production was positively correlated with increased GCF volume, but not with gingival bleeding, visible plaque, or probing depth.ConclusionsAlthough orthodontic treatment with spurs in children resulted in increased gingival bleeding around the mandibular incisors, IL levels were higher around the maxillary incisors and not correlated with periodontal parameters. Increased cytokine levels in GCF may be associated with the initial tooth movement during open bite correction with a passive orthodontic appliance in children.Open bite

Viral Coinfection and Nasal Cytokines in Children With Clinically Diagnosed Acute Sinusitis.

Objective: Children with no pathogenic bacteria in the nasopharynx are unlikely to have acute bacterial sinusitis. We evaluated whether information on clinical presentation, viral co-detection, and mucosal cytokine levels could be used to predict presence of bacteria in the nasopharynx.Method: We obtained nasopharyngeal (NP) swabs from children diagnosed with acute sinusitis. NP swabs were processed for bacterial culture, viral PCR testing, and cytokine expression. We examined whether results of the bacterial culture could be predicted based on the presence of clinical information, presence of viruses or mucosal cytokine levels.Results: We enrolled 174 children; 123 (71%) had a positive culture for potentially pathogenic bacteria and 51 (29%) had normal flora. 122/174 (70%) tested positive for one or more viruses. Compared to children with normal flora, children with pathogenic bacteria were more likely to have viruses (p < 0.01), but this relationship disappeared when we adjusted for age. Children with pathogenic bacteria in their nasopharynx and children with normal flora had similar levels of nasal cytokines.Conclusion: In children with clinically diagnosed acute sinusitis, clinical presentation, levels of nasal cytokines, and presence of viruses do not differentiate children with and without pathogenic bacteria in their nasopharynx.

Changes of Cytokines in Children With Tic Disorder.

Tic disorder (TD) is a common childhood-onset disease associated with abnormal development of brain networks involved in the motor and sensory processing. The underlying pathophysiological mechanisms in TD are still unclear. An involvement of immune mechanisms in its pathophysiology has been proposed. This study investigates the association between the changes of cytokines and the etiology and development of TD. Different expressions of cytokines in a larger number of samples in our study may provide new insights to the field. The levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were evaluated in 1,724 patients who were clinically diagnosed with TD from 1 to 17.5 years old and 550 were from 6 months to 14.5 years old in the control group. We assessed the levels of cytokines according to the patient's medication status and the severity of the disease. Of the cytokines we investigated, the serum IL-6 concentration of children with TD was significantly higher than that of the control group, while the levels of other cytokines were lower in TD patients. In the patient group whose YTGSS score ranged from 1 to 9, the IL-4, IL-10, and IFN-γ levels increased in medication group compared to unmedication group. Our data suggested that the cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) may play an important role in the etiology and the severity in TD. Whether drug intervention in the early stage of tic disorder has a better effect on children needs further research.

Immunologic changes after house dust mite modified rush subcutaneous immunotherapy in allergic rhinitis children.

BackgroundHouse dust mites (HDM) are the major causative allergen for allergic rhinitis. The sole disease-modifying therapy for allergic rhinitis is allergen immunotherapy (AIT). Rush immunotherapy is the accelerated build-up schedules to reach the target maintenance dose.ObjectiveTo evaluate the kinetic changes of peripheral blood CD4+CD25+FOXP3+ regulatory T cells (Treg) and serum cytokines in children undergoing 2-day modified rush HDM AIT.MethodsChildren aged 5–15 years with allergic rhinitis were enrolled for a 2-day modified rush HDM AIT. Peripheral blood CD4+CD25+FOXP3+ Treg, serum interleukin (IL)-4, IL-13, interferon-γ, and IL-10 were measured at baseline, finishing rush, achieving maintenance dose, 6 months, and 12 months after reaching maintenance dose. Specific IgE (sIgE) to HDM was evaluated at baseline and 12 months after getting the maintenance dose. Rhinitis symptoms were assessed daily using a daily card.ResultsA total of 12 children with a mean age of 13 years were enrolled. Rhinitis symptom-free days per month increased significantly after reaching the maintenance dose compared to baseline (from 9.5 days to 19.5 days, p = 0.002), and the maximum improvement was seen at 1 year. The levels of Treg were significantly increased at 6 months after maintenance dose compared to baseline level (6.27%±1.63% vs. 3.83%±1.80%, p < 0.001). After treatment, there were significantly decreased serum IL-13 at 1 year after maintenance but no significant changes in sIgE to HDM. The systemic reaction during AIT occurred 7 episodes from 119 shots (5.9%).ConclusionTwo-day modified rush HDM AIT provides acceptable systemic reactions and increases the number of CD4+CD25+FOXP3+ Treg in children.

Highly accurate multiprotein detection on a digital ELISA platform.

The emerging single-molecule detection platform digital enzyme-linked immunosorbent assay (ELISA) can detect numerous proteins simultaneously at serum concentrations as low as picograms per milliliter. We sought to improve cytokine detection with this platform to aid diagnosis of conditions such as allergy and asthma. We developed a multiple single-molecule detection digital ELISA approach, through the application of encoded magnetic microbeads to simultaneously detect three cytokines in one serum sample. We tested the approach's utility to distinguish asthma-related cytokines in children. Concentrations of interleukin-4 (IL-4) and IL-6 were significantly higher in children with asthma than in healthy controls, while the concentration of interferon-γ (IFN-γ) was significantly lower. Our method has higher accuracy than conventional methods, and our results indicate that the proposed improved high-sensitivity digital ELISA-based diagnosis approach can facilitate early detection and treatment of childhood asthma or related diseases.