Systemic Inflammation In Children Research Articles

Role of Parameters in Whole Blood Analysis as in Indicator of Systemic Inflammation in Children with Rheumatic Valve Diseases.

English Abstract: Abstract Purpose: The most important cause of mortality and morbidity in acute rheumatic fever (ARF) is carditis and rheumatic heart disease (RHD). The aim of this study was to identify markers that may be indicators of chronic inflammation in whole blood analyses in pediatric patients with RHD who regularly received secondary deposilin prophylaxis. Methods: In our study, 100 children with ARF aged between 4 and 18 years were followed up in the pediatric cardiology outpatient clinic of the patient group. The control group consisted of 100 healthy children of the same sex and age as the patient group. All children in the patient group regularly received deposilin prophylaxis every 21 days. Our study included many whole blood parameters that are reported in the literature to represent changes in chronic inflammatory diseases. These parameters were CRP, RDW, PDW, MPV and leukocyte subtypes, neutrophil, lymphocyte, monocyte counts and their ratios (neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte). Results: Leukocyte count, lymphocyte count, basophil count, MLR and basophil count were significantly lower in the patient group than in the control group (p: 0.047, p: 0.023, p: 0.006). In addition, eosinophil count and RDW value were significantly higher in the patient group than in the control group (p: 0.043; p: 0.001). Conclusion: In our study, low leukocyte, lymphocyte, basophil, MLR and higher eosinophil counts indicated that RDW could be effectively used as a marker for regular depositilin prophylaxis in pediatric patients with RHD. German Abstract: Zusammenfassung Zweck: Die wichtigste Ursache für Mortalität und Morbidität bei akutem rheumatischem Fieber (ARF) sind Karditis und rheumatische Herzkrankheit (RHD). Ziel dieser Studie war es, Marker zu identifizieren, die bei Vollblutanalysen bei pädiatrischen Patienten mit RHD, die regelmäßig eine sekundäre Deposilin-Prophylaxe erhielten, Indikatoren für chronische Entzündungen sein können. Methoden: In unserer Studie wurden 100 Kinder mit ARF im Alter zwischen 4 und 18 Jahren in der pädiatrischen kardiologischen Ambulanz der Patientengruppe nachbeobachtet. Die Kontrollgruppe bestand aus 100 gesunden Kindern desselben Geschlechts und Alters wie die Patientengruppe. Alle Kinder in der Patientengruppe erhielten regelmäßig alle 21 Tage eine Deposilin-Prophylaxe. Unsere Studie umfasste viele Vollblutparameter, von denen in der Literatur berichtet wird, dass sie Veränderungen bei chronischen Entzündungskrankheiten darstellen. Diese Parameter waren CRP, RDW, PDW, MPV und Leukozytensubtypen, Neutrophilen-, Lymphozyten-, Monozytenzahlen und ihre Verhältnisse zueinander (Neutrophilen/Lymphozyten, Thrombozyten/Lymphozyten und Monozyten/Lymphozyten). Ergebnisse: Leukozytenzahl, Lymphozytenzahl, Basophilenzahl, MLR und Basophilenzahl waren in der Patientengruppe signifikant niedriger als in der Kontrollgruppe (p: 0,047, p: 0,023, p: 0,006). Darüber hinaus waren Eosinophilenzahl und RDW-Wert in der Patientengruppe signifikant höher als in der Kontrollgruppe (p: 0,043; p: 0,001). Schlussfolgerung: In unserer Studie wiesen niedrige Leukozyten-, Lymphozyten-, Basophilen-, MLR- und höhere Eosinophilenzahlen darauf hin, dass RDW als Marker für eine regelmäßige Depositilinprophylaxe bei pädiatrischen Patienten mit RHD wirksam eingesetzt werden könnte.

Effect of Pre-, Pro-, and Synbiotics on Biomarkers of Systemic Inflammation in Children: A Scoping Review.

Systemic inflammation plays a central role in many diseases and is, therefore, an important therapeutic target. In a scoping review, we assessed the evidence base for the anti-inflammatory effects of pre-, pro-, and synbiotics in children. Of the 1254 clinical trials published in English in Ovid Medline and Cochrane Library PubMed from January 2003 to September 2022, 29 were included in the review. In six studies of healthy children (n = 1552), one reported that fructo-oligosaccharides added to infant formula significantly reduced pro-inflammatory biomarkers, and one study of a single-strain probiotic reported both anti- and pro-inflammatory effects. No effects were seen in the remaining two single-strain studies, one multi-strain probiotic, and one synbiotic study. In 23 studies of children with diseases (n = 1550), prebiotics were tested in 3, single-strain in 16, multi-strain probiotics in 6, and synbiotics in 2 studies. Significantly reduced inflammatory biomarkers were reported in 7/10 studies of atopic/allergic conditions, 3/5 studies of autoimmune diseases, 1/2 studies of preterm infants, 1 study of overweight/obesity, 2/2 studies of severe illness, and 2/3 studies of other diseases. However, only one or two of several biomarkers were often improved; increased pro-inflammatory biomarkers occurred in five of these studies, and a probiotic increased inflammatory biomarkers in a study of newborns with congenital heart disease. The evidence base for the effects of pre-, pro-, and synbiotics on systemic inflammation in children is weak. Further research is needed to determine if anti-inflammatory effects depend on the specific pre-, pro-, and synbiotic preparations, health status, and biomarkers studied.

Exploring systemic inflammation in children with chronic kidney disease: correlates of interleukin 6.

Systemic inflammation (SI) is linked to chronic kidney disease (CKD) progression and multiple complications. Data regarding SI biomarkers in pediatric patients are scarce. This case-control and cross-sectional study investigates the correlation of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), total iron binding capacity (TIBC) and serum albumin to serum interleukin-6 (IL-6). NLR and PLR were measured in 53 patients (median age: 12.9years), including 17 on dialysis and 36 with a median glomerular filtration rate of 39ml/min/1.73m2, and in 25 age and sex-matched healthy controls. Iron profile, serum albumin and IL-6 were measured in the patient group. IL-6 levels > 3rd quartile were classified as high. Patients presented higher NLR and PLR and particularly those on dialysis (p < 0.001 and p = 0.001). We observed a significant correlation between natural logarithm (ln) of IL-6 (lnIL-6) and NLR (rs = 0.344, p = 0.014), serum albumin (rs = -0.350, p = 0.011) and TIBC (rs = -0.345, p = 0.012) after adjustment for CKD stage, while the correlation between lnIL-6 and PLR was not significant (rs = 0.206, p = 0.151). Combination of NLR, serum albumin and TIBC predicted high IL-6 (13 patients) with an AUC of 0.771 (95% CI 0.608-0.943). Pairing of NLR ≥ 1.7 and TIBC ≤ 300μg/dL exhibited the highest sensitivity (76.9%), while incorporating serum albumin ≤ 3.8g/dL along with them achieved the highest specificity (95%) for detecting high IL-6 levels. Both NLR and PLR levels increase in CKD, especially in patients on chronic dialysis. NLR, rather than PLR, along with TIBC and serum albumin, are associated with IL-6 in pediatric CKD.

Low CCL2 and CXCL8 Production and High Prevalence of Allergies in Children with Microcephaly Due to Congenital Zika Syndrome.

Congenital Zika Syndrome (CZS) is associated with an increased risk of microcephaly in affected children. This study investigated the peripheral dysregulation of immune mediators in children with microcephaly due to CZS. Gene expression quantified by qPCR in whole blood samples showed an increase in IFNγ and IL-13 transcripts in children affected with microcephaly compared to the control group. The microcephaly group exhibited significantly decreased CCL2 and CXCL8 levels in serum, quantified by CBA assay. An allergic profile questionnaire revealed a high prevalence of allergies in the microcephaly group. In accordance, elevated serum IgE level measured by the Proquantum Immunoassay was observed in children affected with microcephaly compared to the control group. Altogether, these findings show a persistent systemic inflammation in children with microcephaly due to CZS and suggest a possible impairment in leukocyte migration caused by low production of CCL2 and CXCL8, in addition to high levels of IgE associated with high prevalence of allergies. The dysregulation of inflammatory genes and chemokines underscores the importance of understanding the immunological characteristics of CZS. Further investigation into the long-term consequences of systemic inflammation in these children is crucial for developing appropriate therapeutic strategies and tailored vaccination protocols.

Helicobacter pylori—The Bridge between Local and Systemic Inflammation in Children

Helicobacter pylori (H. pylori)-associated inflammatory status is no longer a debatable topic in children. The aim of our study was to to compare the inflammatory status in pediatric patients with H. pylori gastritis and non-H. pylori gastritis versus control group. We performed a prospective study on 68 children with dyspeptic symptoms which were divided into 3 groups: 14 children with H. pylori gastritis (group 1), 26 children with non-H. pylori gastritis (group 2) and 28 children with no pathological findings—control group (group 3). Several laboratory parameters, histopathological and immunohistochemistry tests were performed in all children for detecting inflammatory status. We noticed a significant difference in terms of rural area between the three groups (p = 0.0404). Comparing the laboratory parameters between the three groups, we noticed significant differences in terms of serological tests (p = 0094), and NLR (p = 0.0253), the latter being significantly higher in children with H. pylori-induced gastritis as compared to those with non-H. pylori gastritis (0.0107). According to the Dunn’s Multiple Comparison Test, we noticed a significantly elevated neutrophil level in children with H. pylori-induced gastritis when compared to non-H. pylori gastritis group (p = 0.0146), as well as a significantly increased eosinophil count in patients with non-H. pylori gastritis as compared to control group (p = 0.0417). The immunohistochemistry method pointed out no significant variation concerning interleukin (IL 6) between children with gastritis and control group [RR = 1.283, IC (95%): 0.9404–1.751, p = 0.0988]. Additionally, children with gastritis regardless of the etiology have a significant risk of associating increased gastric expression of tumor necrosis factor alpha (TNF α) [RR = 3.967; CI (95%): 1.283–12.263; p = 0.0063]. Moreover, TNF α was significantly associated with presence of H. pylori gastritis (p = 0.0002). The early detection of local inflammation triggered by this infection might preempt gastric carcinogenesis, while identifying H. pylori-induced systemic inflammation lowers the risk of severe extraintestinal manifestations.

Innate immune cell dysfunction and systemic inflammation in children with chronic liver diseases undergoing transplantation

Advanced liver diseases (ALD) can affect immune function and compromise host defense against infections. In this study, we examined the phenotypic and functional alterations in circulating monocyte and dendritic cells (DCs) in children with ALD undergoing liver transplantation (LT). Children were stratified into 2 clusters, C1 (mild) and C2 (severe), on the basis of laboratory parameters of ALD and compared with healthy pediatric controls. Children in C2 had a significant reduction in frequencies of nonclassical monocytes and myeloid DCs. Children in C2 displayed monocyte and DC dysfunction, characterized by lower human leucocyte antigen DR expression and reduced interleukin 12 production, and had an increased incidence of infections before and after LT. Children in C2 demonstrated immune dysregulation with elevations of pro- and anti-inflammatory cytokines in plasma. Alterations of innate immune cells correlated with multiple laboratory parameters of ALD, including plasma bile acids. In vitro, monocytes cultured with specific bile acids demonstrated a dose-dependent reduction in interleukin 12 production, similar to alterations in children with ALD. In conclusion, a cohort of children with ALD undergoing LT exhibited innate immune dysfunction, which may be related to the chronic elevation of serum bile acids. Identifying at-risk patients may permit personalized management pre- and post-transplant, thereby reducing the incidence of infection-related complications.

Assessment of Gut leakage Induced Systemic Inflammation in Children on Chronic Hemodialysis

BACKGROUND: Children with chronic kidney disease (CKD) are at high risk to develop GIT complications such as intestinal wall edema and increased permeability which contributes to chronic systemic inflammation that increases morbidity and mortality burden. AIM: This study aim was to show the relationship between inflammation and increased intestinal permeability in children on hemodialysis (HD). METHODS: The study included 50 children with CKD on regular HD of variable duration; their age range was (5−16) years and 40 controls. They were followed up at Nephrology clinic- Eldemerdash hospital. Complete history taking, physical examination were done. Laboratory measurement in the form of zonulin, tumor necrosis factor-alpha (TNF-alpha), high sensitive C-reactive protein (hs-CRP), and alpha1-antitrypsin (AAT) were quantified in serum by ELISA method. RESULTS: There was a highly significant decrease in anthropometric measures (weight, height and BMI) and their corresponding z score in cases compared to controls with p ≤ 0.001. Furthermore, there was significant increase of levels of zonulin, TNF-alpha, AAT, and hs-CRP in cases compared to controls with p value of 0.009, 0.001, 0.002, and 0.003, respectively. There was significant positive correlation between zonulin and (TNF-alpha, AAT, hs-CRP, and creatinine) with P values (0.003, 0.001, 0.001, and 0.001), respectively. Zonulin is negatively correlated with weight for age Z score (WAZ) and height with p value (0.01 and 0.018), respectively. TNF-alpha and hs-CRP were negatively correlated with WAZ with P-values of 0.02 and 0.01, respectively. CONCLUSION: Children with CKD on chronic hemodialysis had elevated levels of zonulin, TNF-alpha, hs-CRP, and AAT which reflects gut permeability induced systemic inflammatory state.

Investigation of the relationship between periodontal and systemic inflammation in children with Sickle Cell Disease: A case- control study.

Periodontal diseases are chronic inflammatory diseases and tissue destruction increases with oxidative stress in periodontal tissues. Periodontal diseases are associated with systemic diseases such as diabetes, cardio-vascular diseases and rheumatoid arthritis by means of systemic inflammation. Sickle cell disease (SCD) is a chronic inflammatory disease in which vaso-occlusive crisis and endothelial dysfunction are present. It is not known whether the chronic systemic inflammation seen in SCD affect periodontal tissues. The aim of this study was to investigate the relationship between periodontal and systemic inflammation in children with SCD. Forty-three children with SCD and 43 healthy children were included in the study. Physical, dental and periodontal statuses were examined, blood and saliva samples were taken. Levels of pro-inflammatory and oxidative stress mediators in serum and saliva were evaluated. The periodontal findings of the groups were similar. The majority of the subjects in both groups had gingival inflammation. In SCD group, significantly higher serum high sensitive C-reactive protein (Hs-CRP), interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, total oxidant status (TOS), nitric oxide (NO) and salivary IL-6 were observed (p<0.05). There were positive correlations between salivary IL-6 levels and serum Hs-CRP levels (r=0.303, p<0.05). In addition; it was determined that salivary IL-6, TNF-α and NO levels were increased 3-6 times in children with a history of painful crisis or acute chest syndrome compared to children who had never had a painful crisis or acute chest syndrome. Although, observed oral health status was similar in both groups, salivary cytokine levels were increased in children with SCD. The higher salivary cytokine levels may be associated with chronic systemic inflammation and vaso-occlusion observed in children with SCD.

Evaluation of a nurse-supervised rehabilitation programme on clinical features and systemic inflammation in Chinese children with asthma: A propensity score-matched analysis.

To evaluate whether a nurse-supervised rehabilitation programmes could improve respiratory functions and systematic inflammation in children with asthma. Children with asthma always suffer from poor life quality, and physical training and pulmonary rehabilitation could be beneficial to asthma. A retrospective, observational, single-centre cohort analysis. Baseline characteristics between the nurse-supervised rehabilitation programme and usual-care groups were matched by propensity-score matching (PSM) in a 1:1 ratio. We compared the lung function and inflammatory markers between groups. Among 52 pairs of children, differences in lung function were improved in the nurse-supervised rehabilitation group compared with those in usual-care group, including the oxygen saturation, forced expiratory volume in 1 second, forced expiratory flow of 25%-75% and peak expiratory flow (all P < 0.05). Two asthma-related inflammatory markers (hypersensitive C-reactive protein and immunoglobulin E) also significantly decreased in the nurse-supervised rehabilitation group (both P < 0.001). The results indicate that the nurse-supervised rehabilitation programme might be effective in improving symptom control, respiratory functions and systemic inflammation in children with asthma. The study suggests that the NSR for asthma merits further research.

The impact of a needs-oriented dental prophylaxis program on bacteremia after toothbrushing and systemic inflammation in children, adolescents, and young adults with chronic kidney disease

BackgroundChronic kidney disease (CKD) still leads to high mortality rates, mainly due to cardiovascular disease. One important influencing factor is persisting low-grade chronic inflammation partly maintained by gingivitis that favors transient bacteremia during daily activities such as toothbrushing.MethodsTo examine whether intensive dental prophylaxis can restore oral health, reduce the prevalence of bacteremia and degree of systemic inflammation indicated by CRP levels, we conducted this pilot study examining 30 CKD patients aged 6–26 years, 15 receiving intensive prophylaxis (IP), 15 receiving treatment as usual (TAU) serving as control group. There were three appointments for examination, each 10 ± 1 weeks apart (at baseline, after intervention periods one and two, when TAU also received IP, and the IP group stopped prophylaxis).ResultsThe gingival index (GI) in the IP group decreased by 90% (GI 0.09; p=0.001), resulting in almost healthy gingiva. There was no significant change in CRP or prevalence of bacteremia. General prevalence of bacteremia after toothbrushing was 9.5% affecting 7 (26%) of the participants. In three participants, bacteremia dissolved after IP, in one after TAU. Two patients developed bacteremia ≥ 10 weeks after ending IP. We identified eight different bacterial species.ConclusionsWe were able to show that IP can effectively treat gingivitis. It might be a promising approach to reduce systemic inflammation and subsequently lower premature cardiovascular disease, despite the lack of statistical significance. Future research requires a larger patient cohort to enable matched treatment groups with long-term follow-up and molecular detection methods for bacteremia.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

The effects of increasing fruit and vegetable intake in children with asthma: A randomized controlled trial.

A high fruit and vegetable (F&V) diet reduces asthma exacerbations in adults; this has not been examined in children to date. To investigate the effect of a 6-month, high F&V diet on the time to first asthma exacerbation in children with asthma, in a parallel-group, randomized, controlled trial. Children (aged 3-11years) with asthma, history of exacerbations and usual low F&V intake (≤3 serves/day) were randomized to the intervention (high F&V diet) or control group (usual diet) for 6months. The primary outcome was time to first exacerbation requiring medical intervention. Secondary outcomes included exacerbation rate, lung function, plasma TNF-α, CRP, and IL-6, faecal microbiota and peripheral blood mononuclear cell (PBMC) histone deacetylase (HDAC) activity and G-protein coupled receptor (GPR) 41/43 and HDAC (1-11) expression. 67 children were randomized between September 2015 and July 2018. F&V intake (difference in change (∆): 3.5serves/day, 95% CI: [2.6, 4.4] p<0.001) and plasma total carotenoids (∆: 0.44µg/ml [0.19, 0.70] p=0.001) increased after 6months (intervention vs control). Time to first exacerbation (HR: 0.81, 95% CI: [0.38, 1.69], p=0.569; control vs. intervention) and exacerbation rate (IRR: 0.84, [0.47, 1.49], p=0.553; control vs. intervention) were similar between groups. In per-protocol analysis, airway reactance z-scores increased in the intervention versus control group (X5 ∆: 0.76 [0.04, 1.48] p=0.038, X20 ∆: 0.93 [0.23, 1.64] p=0.009) and changes in faecal microbiota were observed though there was no difference between groups in systemic inflammation or molecular mechanisms. In the control group, CRP and HDAC enzyme activity increased, while GPR41 expression decreased. No adverse events attributable to the interventions were observed. A high F&V diet did not affect asthma exacerbations over the 6-month intervention, though warrants further investigation as a strategy for improving lung function and protecting against systemic inflammation in children with asthma.

The effect of dexmedetomidine premedication on postoperative systemic inflammatory response in children undergoing hernia repair surgery: A randomized controlled trial.

BackgroundSurgery results in systemic inflammation, which can affect the central nervous system, leading to changes in mood, emotion, and behavior. Our previous study has shown that compared to midazolam, dexmedetomidine premedication effectively decreased children's postoperative anxiety.AimTo investigate whether dexmedetomidine infusion before hernia repair alleviates postoperative systemic inflammation in children and whether postoperative anxiety may be associated with postoperative inflammation.MethodsThis prospective double‐blind randomized controlled trial was conducted in 120 children scheduled to undergo elective hernia repair. Before anesthesia induction, all children received an intravenous infusion consisted of dexmedetomidine (n = 40; 0.5 µg/g, group D), midazolam (n = 40; 0.08 mg/kg, group M), or normal saline (n = 40; group C). One‐way ANOVA with least significant difference multiple comparison test was used for multigroup comparisons of postoperative plasma levels of inflammatory cytokines and m‐YPAS scores. Spearman rank correlation tests were used for analyzing m‐YPAS scores with postoperative plasma levels of inflammatory cytokines.ResultsPlasma levels of tumor necrosis factor‐alpha (7.0 ± 1.6 vs. 8.1 ± 1.6, mean difference [95% CI]: 1.19 [0.26–2.11], p = .008) (pg/ml) and of interleukin‐6 (1.8 ± 1.2 vs. 3.3 ± 1.6, mean difference [95% CI]: 1.49 [0.74–2.25], p < .001) (pg/ml) and neutrophils‐to‐lymphocyte ratio (1.0 ± 0.5 vs. 1.5 ± 0.7, mean difference [95% CI]: 0.48 [0.17–0.78], p < .001) were significantly lower in group D than in group C. Furthermore, compared to group M, group D showed significantly lower plasma tumor necrosis factor‐alpha levels (7.0 ± 1.6 vs. 7.9 ± 1.9, mean difference [95% CI]: 0.96 [0.04–1.88], p = .04) (pg/ml) and interleukin‐6 levels (1.8 ± 1.2 vs. 2.9 ± 1.5, mean difference [95% CI]: 1.06 [0.31–1.81], p = .004) (pg/ml), and neutrophil‐to‐lymphocyte ratio (1.0 ± 0.5 vs. 1.5 ± 0.6, mean difference [95% CI]: 0.42 [0.11–0.72], p = .004). Anxiety scores at postoperative 2 and 4 h in the three groups positively correlated with plasma levels of proinflammatory cytokines.ConclusionA single preoperative intravenous dexmedetomidine dose in children undergoing same‐day surgery reduces postoperative systemic inflammation.

Mean Platelet Volume and Platelet Function in Neonatal Sepsis

Background: Neonatal sepsis is a clinical disorder developed by bacterial blood stream infections in neonates. CBC indices, such as platelet count, mean platelet volume (MPV), PDW have been used as markers of systemic inflammation in children and adults. Objective: To assess MPV and platelets function in neonatal sepsis. Patients and Methods: This study was a case control, which included 50 cases and 50 controls. All participants were subjected to history taking, clinical examination, CBC, C-reactive protein, blood cultures and assessment of mean platelets volume. Results: There was a significant decrease in haemoglobin level, RBCs count, and platelet count. While, there was significant increase in WBCs count and MPV in the patient group than in the control group. Mean value of platelet count was statistically significantly lower among cases than in control. MPV was significantly higher in patients than controls. PDW was statistically significantly lower among cases than in controls. MPV showed significant negative correlation with gestational age, birth weight and platelet count. While it showed statistically significant positive correlation with CRP. Conclusion: Mean value of platelet count and PDW were statistically significant lower among cases than in control while MPV was significantly higher in patients than in controls. So, platelet function could be a useful early diagnostic marker in neonatal sepsis.

Mean Platelet Volume and Platelet Function in Neonatal Sepsis

Background: Neonatal sepsis is a clinical disorder developed by bacterial blood stream infections in neonates. CBC indices, such as platelet count, mean platelet volume (MPV), PDW have been used as markers of systemic inflammation in children and adults. Objective: To assess MPV and platelets function in neonatal sepsis. Patients and Methods: This study was a case control, which included 50 cases and 50 controls. All participants were subjected to history taking, clinical examination, CBC, C-reactive protein, blood cultures and assessment of mean platelets volume. Results: There was a significant decrease in haemoglobin level, RBCs count, and platelet count. While, there was significant increase in WBCs count and MPV in the patient group than in the control group. Mean value of platelet count was statistically significantly lower among cases than in control. MPV was significantly higher in patients than controls. PDW was statistically significantly lower among cases than in controls. MPV showed significant negative correlation with gestational age, birth weight and platelet count. While it showed statistically significant positive correlation with CRP. Conclusion: Mean value of platelet count and PDW were statistically significant lower among cases than in control while MPV was significantly higher in patients than in controls. So, platelet function could be a useful early diagnostic marker in neonatal sepsis.

Cortisol and laboratory indicators of systemic inflammation in case of bacterial purulent meningitis and viral encephalitis in children

Pediatric bacterial purulent meningitis (BPM) and viral encephalitis (VE) are significant medical and social problems due to their course severity, high frequency of death cases, and formation of neurologic deficiency at the disease outcome. Activation of hormonal regulation and severity syndrome of systemic inflammatory response are important factors to evaluate the character of BPM and VE course.Objective.To study the level of cortisol and laboratory indicators of systemic inflammation in children with various variants of BPM and VE course depending on the period of the disease (acute period, reconvalescence) to specify their role in the pathogenesis of acute neuroinfections.Object and methods.There were investigated hematological indicators, the level of cortisol, C-reactive protein in blood serum of 60 children, 39 of them had BPM and 21 ones VE. The comparison group included 14 children aged from 1 to 14 years old who were undergoing rehabilitation care due to neurologic problems at the Federal State-Financed Institution Pediatric Research and Clinical Center for Infectious Diseasesunder the Federal Medical Biological Agency.Results.The patients were divided into some subgroups according to the severity of their condition at the moment of hospitalization, i.e. urgent condition or critical condition requiring organ replacement therapy. The maximum increase of cortisol level and laboratory markers of systemic inflammation during the acute period was revealed in case of BPM in comparison with VE with a subsequent normalization to the stage of reconvalescence. Thelevel of cortisol during the acute period of BPM was reliably higher in the subgroup with urgent conditions, whereas in case of VE in the subgroup with critical conditions. There were no significant differences in the laboratory indicators of systemic inflammation response among the subgroups. There was established a correlation interrelation of cortisol level and the content of granulocytes and blood lymphocytes.Conclusion.There were identified characteristic features of cortisol content in children with bacterial and viral neuroinfections depending on the course of the disease.

Early-life air pollution exposure and biomarkers of systemic inflammation in young children

Background/Aims. Air pollution exposure has been associated with adverse health effects in children. Although the exact underlying mechanisms are not clarified, systemic inflammation may play a role in pollution-induced health effects. This study aimed to investigate inflammatory markers in children in relation to early-life air pollution exposure. Methods. We measured 92 inflammatory markers in plasma samples collected at ages 6 months, 1 and 2 years from healthy children residing in Stockholm, Sweden (n=108), using Olink Proteomics (Uppsala, Sweden). Residential time-weighted average (TWA) outdoor exposure to particulate matter with an aerodynamic diameter of &lt;10 μm (PM10) and &lt;2.5 μm (PM2.5), black carbon (BC), nitrogen oxides (NOx) and nitrogen dioxide (NO2) from birth up to age 6 months was estimated by dispersion modeling. Age-specific associations between TWA air pollution exposures and inflammatory markers were investigated using linear regression with inclusion of potential confounding variables. Further, we applied linear mixed-effect models to analyze the temporal patterns of biomarkers during the first 2 years of life in relation to early-life air pollution exposure. Multiple comparisons were accounted for using False Discovery Rate (FDR 5%) adjustment. Results. At age 1 year, tumor necrosis factor (TNF) and chemokine ligand 9 (CXCL9) were inversely associated with TWA exposure to NO2, NOx, and BC (FDR p-value&lt;0.05). However, no clear association was found at ages 6 months or 2 years. In the mixed models, only TNF was associated with NO2, NOx, and BC, but the associations were not significant after adjustment for multiple testing. Conclusions: Our findings suggest that air pollution exposure during the first 6 months of life is related to certain markers of systemic inflammation in children at age 1 year. These markers may be involved in biological processes through which air pollution exposure may modulate systemic inflammation in infants.

Antioxidant activity of Hydroxytyrosol and Vitamin E reduces systemic inflammation in children with paediatric NAFLD

BackgroundThe rise in paediatric non-alcoholic fatty liver disease (NAFLD) is particularly alarming. We recently reported that Hydroxytyrosol (HXT) and Vitamin E (VitE) may improve oxidative stress, insulin resistance, and steatosis in children with biopsy-proven NAFLD. AimHere, we investigated if HXT+VitE may reduce systemic inflammation in the above-mentioned patients. MethodsThis study analysed the plasma levels of IL (interleukin)-6, IL-1β, IL-10, tumour necrosis factor (TNF)-α, 4‑hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2′deoxyguanosine (8-OHdG) in children enrolled in the HXT+VitE trial (ClinicalTrials.gov, NCT02842567). ResultsChanges in markers of systemic inflammation were found in both placebo (Pla) and HXT+VitE. In particular, after four months, the levels of IL-1β and TNF-α were reduced in both groups, while IL-6 decreased, and IL-10 increased significantly only in the group treated with HXT+VitE. Children treated with HXT+VitE showed a significant decrease of 4-HNE and 8-OHdG that correlated with the improvement of triglyceride levels. Noticeably, only the 8-OHdG decrease correlated with steatosis amelioration and with the increase of IL-10 levels. ConclusionThe treatment with HXT and VitE reduced the NAFLD-related systemic inflammation in children, mainly by an increase of IL-10 circulating levels that occurred in response to DNA damage recovery, ultimately improving steatosis and hypertriglyceridemia.

Altered gut microbiota correlated with systemic inflammation in children with Kawasaki disease

Kawasaki disease (KD) is a multi-systemic vasculitis of unknown etiology that occurs mainly in children, and the disturbance of gut microbiota is generally believed to cause a hyperimmune reaction triggering KD. The aim of the study was to investigate the alterations in the fecal microbiota and assess its relationship with systemic inflammation. Totally 30 KD children were enrolled and followed up for 6 months, with another group of 30 age- and sex-matched healthy children as controls. Phylotype profiles of fecal microbial communities were analyzed using 16S rRNA gene sequencing. Serum inflammatory markers were detected by flow cytometer. We showed that KD children exhibited a significant reduction in fecal microbial diversity in the acute phase compared with the healthy controls. Enterococcus, Acinetobacter, Helicobacter, Lactococcus, Staphylococcus and Butyricimonas in acute KD children were significantly higher than the healthy children. Levels of systemic inflammation biomarkers, including IL-2, IL-4, IL-6, IL-10, TNF-α, and INF-γ, were significantly elevated in the acute KD children. Altered microbiota genera Enterococcus and Helicobacter abundances were shown to be correlated positively with IL-6, which were never previously reported in KD. This study suggested that gut microbiota alteration is closely associated with systemic inflammation, which provides a new perspective on the etiology and pathogenesis of KD.

1271-P: Plasma Calprotectin Is Associated with Obesity and Systemic Inflammation in Children

Purpose: Childhood obesity is a major risk factor for many chronic diseases including type 2 diabetes and cardiovascular disease. Plasma calprotectin is elevated in various inflammatory disorders, including obesity-associated low-grade inflammation. We measured the level of plasma calprotectin in obese children and assessed its association with key metabolic and inflammatory biomarkers. Methods: The study included a total of 76 children (age 9.8±2.43 years), which were grouped according to the body mass index (BMI) into 3 groups: normal-weight (BMI &amp;lt;85th percentile; n=12), over-weight (BMI 85-94th percentile; n=2) and obese (BMI ≥95th percentile, n=62). The plasma levels of metabolic and inflammatory biomarkers were quantified using commercially available ELISA kits. Results: Calprotectin was directly correlated with the BMI (r=0.4, P=0.001, n=69), BMI percentile (r=0.5, P &amp;lt;0.0001, n=69), and BMI Z-score (r=0.5, P&amp;lt;0.0001, n=69). Calprotectin was directly correlated with body fat (%; r=0.3, P=0.02, n=63) and fat to muscle ratio (r=0.32, P=0.02, n=50) but inversely correlated with muscle (%) (r= ? 0.3, P=0.03, n=50). Calprotectin was inversely correlated with adiponectin (r= ? 0.3, P=0.04, n=57) but directly correlated with leptin (r=0.4, P=0.0005, n=75), and leptin to adiponectin ratio (r=0.45, P=0.0005, n=56). Calprotectin was directly correlated with CRP (r=0.4, P=0.003, n=54), IL-6 (r=0.44, P&amp;lt;0.0001, n=76) and MCP-1 (r=0.3, P=0.02, n=76). Calprotectin was also directly correlated with resistin (r=0.3, P=0.02, n=76). Children with obesity (n=62) had significantly (P&amp;lt;0.0001) higher levels of calprotectin compared to those with normal-weight (n=12). In the obese state, males (n=30) had significantly (P=0.03) higher levels of calprotectin compared to females (n=32). Conclusion: Plasma calprotectin is elevated in children with obesity and is correlated with key metabolic and inflammatory biomarkers. Disclosure A. Hasan: None. S.P. Kochumon: None. Funding Kuwait Foundation for the Advancement of Science (RA-2011-018)

Relationships Among and Predictive Values of Obesity, Inflammation Markers, and Disease Severity in Pediatric Patients with Obstructive Sleep Apnea Before and After Adenotonsillectomy.

Both obstructive sleep apnea (OSA) and obesity are major health issues that contribute to increased systemic inflammation in children. To date, adenotonsillectomy (AT) is still the first-line treatment for childhood OSA. However, the relationships among and predictive values of obesity, inflammation, and OSA severity have not been comprehensively investigated. This prospective study investigated body mass index (BMI), serum inflammatory markers, and OSA severity before and after AT in 60 pediatric patients with OSA. At baseline, differences in levels of interleukin-6, interleukin-9, basic fibroblast growth factor, platelet-derived growth factor-BB, as well as regulated on activation, normal T cell expressed and secreted (RANTES) were significant among the various weight status and OSA severity subgroups. After 3 months postoperatively, the differences in these inflammatory markers diminished along with a decrease in OSA severity while obesity persisted. The rate of surgical cure (defined as postoperative obstructive apnea-hypopnea index < 2.0 and obstructive apnea index < 1.0) was 62%. Multivariate analysis revealed that age, BMI z-score, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein-1, and RANTES independently predicted surgical cure. Despite the significant reductions in inflammatory markers and OSA severity after AT, an inter-dependent relationship between obesity and OSA persisted. In addition to age and BMI, several inflammatory markers helped to precisely predict surgical cure.