Hepcidin and inflammation associated with iron deficiency in childhood obesity - A systematic review

Abstract Objectives: This paper aims to review data on the association of obesity and iron deficiency in children and adolescents, exposing the possible involvement of hepcidin and interleukin-6 (IL-6), obesity's inflammation biomarkers. Data source: Articles from PUBMED and WEB OF SCIENCE database with no chronological limit were reviewed to write this systematic review. Keywords such as children, obesity, iron deficiency, and hepcidin were used. After deleting duplicated and review articles, 91 were screened, and 39 were selected as eligible. Sixteen articles were included because they involved serum hepcidin levels in obese children and adolescents as outcomes. Summary of findings: Finally, those 16 articles were organized in two tables: one includes therapeutic interventions, and the other does not. As hepcidin was discovered in 2000, the first articles that presented serum hepcidin's quantification in obese children and adolescents, homeostasis iron markers, and their possible association with obesity's inflammatory environment began to be published in 2008. Conclusions: Obesity's chronic inflammation state leads to the production of IL-6, which acts as a signaling molecule for hepcidin synthesis, resulting in iron deficiency, which is common in obese children and adolescents who respond inadequately to iron supplementation. On the other hand, that population responds adequately to therapeutic intervention programs that lead to weight loss, guaranteeing iron homeostasis improvement. Therefore, perhaps it is time to discuss serum hepcidin level quantification as part of evaluating children and adolescents with iron deficiency, which could guide clinical choices that might lead to better therapeutic outcomes.

The clinicopathologic and immunohistochemical features of 60 cutaneous glomus tumor: a retrospective case series study

Abstract Background Glomus Tumor (GT) are benign neoplasms that originate from mesenchymal cells. It presents as tenderness and cold allodynia in the digits, especially in the subungual region. There are a few studies that investigated the mechanism of pain. Objectives To analyze the clinical-pathologic characteristics of GT and to identify the expression of IL-1β, IL-6, and CGRP in it, further, to explore the possible mechanism of pain. Methods The clinical and pathological data of 60 GT patients were retrospectively analyzed. Tissue microarrays and immunohistochemistry were used to measure the expression of IL-1β, IL-6 and CGRP. Results GT is more common in females and the ratio of male to was near to 1:2, mostly in middle-aged people. It often occurs in fingertips, especially the thumbs. Patients often present with spontaneous pain, tenderness, and cold hypersensitivity. Both the two pain mediators IL-1β and IL-6 were highly expressed in GT cells of patients with and without cold hypersensitivity. While CGRP was not expressed in GT. Study limitations Low sample size and further research is needed to explore the specific mechanism. Conclusions IL-1β and IL-6 were highly expressed in GT cells, suggesting that IL-1β and IL-6 have certain nociceptive roles in GT. In the 4 patients with cold intolerance, the intensity of IL-1β and IL-6 staining was also strong, suggesting that they may not play a role in the cold hypersensitivity. However, since there are only 4 patients with cold intolerance, it's necessary to conduct further in-depth research using a larger sample size. The specific role of CGRP in GT has not been found yet.

Effect of submucosal cryotherapy compared with steroids and NSAIDs injections on Substance P and Interleukin 6 pulpal release in experimentally induced pulpal inflammation in rabbits

Abstract Objective To compare the effect of submucosal cryotherapy using cold saline to dexamethasone sodium phosphate and diclofenac sodium injections on substance P and interleukin 6 release in experimentally induced pulpal inflammation in rabbits' molar teeth. Methodology Fifteen rabbits were randomly classified into 3 groups according to the submucosal injection given: cold saline, dexamethasone sodium phosphate, and diclofenac sodium. A split-mouth design was adopted, the right mandibular molars were experimental, and the left molars served as the control without injections. Intentional pulp exposures were created and left for 6 hours to induce pulpitis. Pulpal tissue was extracted and examined for SP and IL-6 levels using ELISA. Within each group, the level of cytokines released was measured for both control and experimental groups for intragroup comparison to determine the effect of injection. The percentage reduction of each mediator was calculated compared with the control side for intergroup comparison then the correlation between SP and IL-6 levels was analyzed using Spearman's rank order correlation coefficient. Statistical analysis was performed, and the significance level was set at p<0.05. Results Submucosal cryotherapy, dexamethasone sodium phosphate, and diclofenac sodium significantly reduced SP and IL-6 pulpal release. Submucosal cryotherapy significantly reduced SP more than and IL-6 more than dexamethasone sodium phosphate and diclofenac sodium. Pulpal reduction of SP and IL-6 showed a strong positive significant correlation. Conclusions Submucosal cryotherapy reduces the pulpal release of SP and IL-6 and could be tested as an alternative to premedication to potentiate the effect of anesthesia and control postoperative endodontic pain.

Genetic polymorphism of interleukins 6 and 17 correlated with apical periodontitis: A Cross-sectional study

Abstract Interleukins 6 and 17 act in bone resorption in the presence of infections of endodontic origin for host defense. Genetic polymorphisms may be associated with increased bone loss, represented by areas of large periapical lesions. This study aimed to verify the frequency of interleukin 6 and 17 gene polymorphism in patients with asymptomatic apical periodontitis or chronic apical abscess and to verify the existence of correlations between periapical lesion area with age, gender, and presence of the polymorphism, in the studied population, in the state of Pernambuco. A population consisting of thirty diagnosed individuals was included. The area of the lesions was measured in mm². Genomic DNA was extracted and genotyping was performed by Polymerase Chain Reaction Restriction Fragment Length Polymorphism for interleukin 6 (rs 1800795) and interleukin 17 (rs 2275913). Fisher's exact, chi-square, and odds ratio tests were used. A logistic regression analysis was also performed using sex, age, and the presence of polymorphism as covariates, in addition to linear regression to test the relationship between age and lesion area. All tests used a significance level of 0.05% (p ≤0.05%). There was no statistical significance in the occurrence of large areas of periapical lesions correlated with age, sex, and diagnosis, nor in the distribution of alleles in the polymorphism of interleukins 6 and 17 in the studied groups. The frequency of homozygous and heterozygous polymorphism was high. The polymorphism of these interleukins is not correlated with the increase in the areas of asymptomatic periapical inflammatory lesions.

Resumo As interleucinas 6 e 17 atuam na reabsorção óssea na presença de infecções de oriegem endodôntica para defesa do hospedeiro. Polimorfismos genéticos podem estar associados ao aumento da perda óssea, representada por áreas de lesões periapicais grandes. O objetivo deste estudo foi verificar a frequência do polimorfismo dos genes interleucina 6 e 17 em pacientes com periodontite apical assintomática ou abscesso apical crônico e verificar a existência de correlações entre área de lesão periapical com idade, sexo e presença do polimorfismo, na população estudada, no estado de Pernambuco. Foi incluída uma população constituída por trinta indivíduos diagnosticados. A áreas da lesões foram medidas em mm². O DNA genômico foi extraído e a genotipagem realizada por Polimorfismo de Comprimento de Fragmento de Restrição de Reação em Cadeia da Polimerase para interleucina 6 (rs 1800795) e interleucina 17 (rs 2275913). Os testes exato de Fisher, qui-quadrado e odds ratio foram utilizados. Uma análise de regressão logística também foi realizada usando sexo, idade e presença de polimorfismo como covariável, além de regressão linear para testar a relação da idade e área da lesão. Todos os testes utilizaram um nível de significância de 0,05% (p ≤0.05%). Não houve significância estatística na ocorrência das áreas grandes de lesões periapicais correlacionadas com idade, sexo e diagnóstico nem nas distribuições de alelos no polimorfismo das interleucinas 6 e 17 nos grupos estudados. A frequência de polimorfismo homozigoto e heterozigoto foi alta. O polimorfismo dessas interleucinas não está correlacionado ao aumento das áreas das lesões inflamatórias periapicais assintomáticas.

Effect of obesity, lipids and adipokines on allergic rhinitis risk: a Mendelian randomization study

Abstract Objectives: Observational studies suggested that obesity may promote the development of allergic rhinitis. The aim of this study was to explore the association of obesity, lipids and adipokines with this allergic disease at the genetic level using Mendelian randomization strategies. Methods: Summary data for three obesity indicators (such as body mass index), eight lipid indicators (such as triglycerides) and six adipokines (such as interleukin-6 and adipocyte fatty acid-binding protein) were collected, and suitable instrumental variables were extracted from these summary data according to the three main assumptions of Mendelian randomization. Three Mendelian randomization methods (such as inverse variance weighted) were used to detect the casual effect of the above indicators on allergic rhinitis risk. Sensitivity analyses were performed to assess heterogeneity and horizontal pleiotropy. Results: After Bonferroni correction, the inverse variance weighted reported that elevated levels of interleukin-6 and adipocyte fatty acid-binding protein were nominally associated with the decreased risk of allergic rhinitis (OR = 0.870, 95% CI 0.765-0.990, p = 0.035; OR = 0.732, 95% CI 0.551-0.973, p = 0.032). The other Mendelian randomization methods supported these results. Obesity, lipids and other adipokines were not related to this allergic disease. Sensitivity analyses found no heterogeneity and horizontal pleiotropy in the study. Conclusion: The study provided some interesting, but not sufficient, evidence to suggest that interleukin-6 and adipocyte fatty acid-binding protein might play a protective role in the development of allergic rhinitis at the genetic level. These findings should be validated by more research. Level of evidence: This was a Mendelian randomized study with a level of evidence second only to clinical randomized trials, and higher than cohort and case-control studies.

Utilización precoz de tocilizumab en pacientes internados con COVID-19 grave y crítica: un estudio multicéntrico en la Provincia de Buenos Aires / Early use of tocilizumab in hospitalized patients with severe and critical COVID-19 in the Province of Buenos Aires: a multicentric study

Resumen Introducción: El objetivo principal del estudio fue evaluar la mortalidad en los pacientes con COVID-19 graves y críticos, que recibieron tocilizumab (TCZ) -un antagonista monoclonal del receptor de IL-6- de forma temprana vs. tardía. Métodos: Cohorte retrospectiva multicéntrica de pacientes >18 años internados con COVID-19 desde el 1/7/2021-1/8/2022, con 5-7 puntos de gravedad inicial (GI) según Escala de la OMS. Se consideró adminis tración temprana o tardía a la infusión de TCZ ≤ ó > a 48 h del ingreso. Las variables de resultado fueron mortalidad a 28 días y cambio de la GI. Los factores relacionados con la mortalidad fueron evaluados con regresión de Cox. Resultados: Se incluyeron 266 pacientes, 159(60%) varones; edad 58(± 15); con hipertensión arterial (43%), obesidad (37%) y diabetes (27%);70 presentaban GI = 5 (oxígeno suplementario), 143 GI = 6 (ventilación no inva siva o cánula nasal de alto flujo) y 53 GI = 7 (ventilación mecánica invasiva). La mortalidad a 28 días fue 42%, asociada independientemente a: edad, obesidad, GI, días entre la internación y administración del TCZ, y días entre la fecha de inicio de síntomas y el TCZ. La mortalidad para GI 5, 6 y 7 fue 26%, 39% y 72%, respectivamente; 76% y 62% de los pacientes permanecieron estables o mejoraron la GI a los días 3 y 7 de la infusión de TCZ. La mortalidad a 28 días fue 39% (TCZ temprano) vs. 57% (TCZ tardío); p = 0.02; HR = 0.63[0.41-0.99, p = 0.05]). Discusión: Estos resultados apoyan la administración temprana de TCZ en pacientes con COVID-19 grave y crítica.

Abstract Introduction: Tocilizumab (TCZ), an IL-6 receptor antagonist monoclonal antibody is warranted in severe and critically-ill COVID-19 patients. The objective was to evaluate 28-day mortality of patients with severe or critical COVID-19 treated with early vs delayed TCZ. Methods: Multicenter, retrospective cohort study in cluding patients>18 years hospitalized between 7/1/2021- 8/1/2022 with confirmed COVID-19, with 5, 6 and 7 points of WHO Ordinal Initial Severity Scale [SS]. Early or late administration was considered if TCZ was administered before or after 48 hours from admission. Outcomes were28-day mortality and change of SS. Factors related to 28-day mortality were evaluated with Cox regression. Results: 266 patients were included, 159(60%) male; aged 58(± 15); frequent comorbidities were hypertension (42%), obesity (37%) and diabetes (27%). Seventy patients had a SS = 5 (Supplemental O2), 143 had SS = 6 (NIV/ HFNC), and 53 had SS = 7 (IMV). 28-day mortality was 42%(112/266); predictors were age, obesity, higher SS, days between hospitalization and TCZ administration, and fewer days between symptoms onset and TCZ. Mortality of SS 5, 6 and 7 was 26%, 39% and 72% respectively. Com pared with baseline SS points, 76% and 62% of patients remained stable or improved on days 3 and 7 since TCZ administration. 28-day mortality was lower when TCZ was administered before 48 hours (39% vs 57%; p = 0.02; HR = 0.63;[0.41-0.99, p = 0.05]). Discussion: This study supports the early use of TCZ in patients with severe or critical COVID-19.

Inflammation in Cardiovascular Disease: Current Status and Future Perspectives

Abstract Atherosclerosis has been defined as an inflammatory disease. Three decades of research have pointed to a pivotal role of interleukin 6 for many aspects of cardiovascular disease, not the least of which is atherosclerosis. In this review, experimental and clinical studies are reported on a timeline, exploring mechanisms and possible explanations that form the basis of current knowledge. Some successful clinical trials were proof of concept studies, showing that not only inflammatory biomarkers are related to cardiovascular outcomes, but also that decreasing inflammation can reduce cardiovascular events. Great advances have been made in the management of residual cardiovascular risk due to cholesterol, thrombosis, and metabolic diseases, but the next frontier now seems to be targeting inflammation. In the upcoming years, the importance of inflammation will be evaluated in high-risk patients with chronic kidney disease, after acute coronary heart disease or heart failure with preserved ejection fraction. Inflammation seems to precede the development of cardiovascular risk factors. Moreover, counseling for a heathy lifestyle and, when necessary, the use of cardiometabolic therapies capable of decreasing inflammation, might be important.

Serum interleukin-6 levels are increased in post-herpetic neuralgia: a single-center retrospective study

Abstract Background: Studies have shown that the overall incidence rate of herpeszoster (HZ) in China is 6.64 cases per 1000 people, despite such harms brought by postherpetic neuralgia (PHN), the mechanism of the disease remains unclear in China. Currently, effective biomarkers to predict PHN remain unavailable, which makes it difficult to prevent and successfully treat PHN. Objectives: The aim of the study was to determine the serum interleukin-6 level in PHN. Methods: The serum levels of interleukin 6 (IL-6) were measured by multi-antibody sandwich ELISA. The likert scale was used to represent the degree of neuralgia in the patients. Patients with PHN were divided into a mild PHN group and a severe PHN group according to the Likert scale. ROC curve was performed for evaluating the diagnostic efficiency of IL6 for PHN. The correlation between the IL6 level and the Likert scale before and after treatment with gabapentin and mecobalamin was analyzed. Results: IL6 levels in PHN patients resulted higher compared to volunteers. Patients in the severe PHN group had a higher serum IL6 level than in the mild PHN group. The Likert scale score was related to the serum IL6 levels and the frequency of IL6 levels above the cutoff value (4.95pg/mL) in PNH groups before and after treatment (p<0.05). Study limitations: Pain is subjective. Some mental states, such as anxiety and depression, greatly influence an individual's perception of pain, and pain tolerance can vary between people. Therefore, pain scores can be affected by different individual factors. Conclusions: The serum IL6 levels may be used as a biochemical indicator of the severity of PNH.

Efecto del estímulo masticatorio y estrés agudo sobre la interleuquina 6, la memoria y el aprendizaje espacial en ratones Balb/c

Introducción. El estrés agudo altera la memoria y aprendizaje espacial y la expresión de la interleuquina 6 (IL-6), mientras que el estímulo masticatorio evitaría dichos efectos. Objetivo. Determinar el efecto del estímulo masticatorio y el estrés agudo sobre la expresión de interleuquina 6, la memoria y el aprendizaje espacial en ratones. Métodos. Experimento con 70 ratones albinos machos de 2 meses de edad de la cepa Balb/c que fueron distribuidos aleatoriamente en grupo A1: estrés agudo 1 hora; grupo A2: estrés agudo 1 hora + estímulo masticatorio 1 hora; grupo B1: estrés agudo 2 horas; grupo B2: estrés agudo 2 horas + estímulo masticatorio 2 horas; grupo C1: estrés agudo 3 horas; grupo C2: estrés agudo 3 horas + estímulo masticatorio 3 horas; y grupo D: sin intervención. Durante 3 días, se evaluó la memoria y el aprendizaje espacial en el laberinto acuático de Morris. La IL-6 fue determinada mediante ELISA. Resultados. La IL-6 fue mayor en el grupo B2 vs los demás grupos (p < 0,001). Además, en el primer día de evaluación, la adquisición de memoria y aprendizaje espacial fue menor en el grupo A1 vs A2 (p = 0,042). Conclusión. Solo en el primer día de evaluación encontramos que el estímulo masticatorio previno la disminución de la adquisición de memoria y aprendizaje espacial en ratones sometidos a estrés agudo de baja intensidad. Los resultados en general no fueron concluyentes sobre el efecto del estímulo masticatorio. Además, la IL-6 fue mayor en el estrés + el estímulo masticatorio (grupo B2) sobre el resto.

Introduction. Acute stress alters memory and spatial learning and the expression of interleukin 6, the chewing stimulus would prevent these effects. Objective. To determine the effect of chewing stimulation and acute stress on the expression of interleukin 6 and memory and spatial learning in mice. Methods. Experiment where 70 male albino mice of the Balb/c of age 2 month were randomly distributed into: Group A1: acute stress 1 hour; Group A2: acute stress 1 hour + chewing stimulus 1 hour; Group B1: acute stress 2 hours; Group B2: acute stress 2 hours + chewing stimulus 2 hours; Group C1: acute stress 3 hours; C2: acute stress 3 hours + chewing stimulus 3 hours; Group D: without intervention. For 3 days, spatial memory and learning were tested in the Morris water maze. Interleukin 6 (IL-6) was analyzed by ELISA test. Results. IL-6 was higher in the B2 group vs the other groups (p<0.0001). In addition, on the first day of evaluation, the acquisition of spatial memory and spatial was lower in the A1 vs. A2 group (p=0.042). Conclusión. Only on the first day of evaluation, we found that the masticatory stimulus prevented the decrease in memory acquisition and spatial learning in mice subjected to low-intensity acute stress. The results were generally inconclusive on the effect of masticatory stimulation. In addition, IL-6 was higher in the stress + masticatory stimulus (group B2) over the rest.

Morphofunctional analysis of fibroblast-like synoviocytes in human rheumatoid arthritis and mouse collagen-induced arthritis

Abstract Background Fibroblast-like synoviocytes (FLS) play a prominent role in rheumatoid synovitis and degradation of the extracellular matrix through the production of inflammatory cytokines and metalloproteinases (MMPs). Since animal models are frequently used for elucidating the disease mechanism and therapeutic development, it is relevant to study the ultrastructural characteristics and functional responses in human and mouse FLS. The objective of the study was to analyze ultrastructural characteristics, Interleukin-6 (IL-6) and Metalloproteinase-3 (MMP-3) production and the activation of intracellular pathways in Fibroblast like synoviocytes (FLS) cultures obtained from patients with rheumatoid arthritis (RA) and from mice with collagen-induced arthritis (CIA). Methods FLSs were obtained from RA patients (RA-FLSs) (n = 8) and mice with CIA (CIA-FLSs) (n = 4). Morphology was assessed by transmission and scanning electron microscopy. IL-6 and MMP-3 production was measured by ELISA, and activation of intracellular signaling pathways (NF-κB and MAPK: p-ERK1/2, p-P38 and p-JNK) was measured by Western blotting in cultures of RA-FLSs and CIA-FLSs stimulated with tumor necrosis factor-alpha (TNF-α) and IL-1β. Results RA-FLS and CIA-FLS cultures exhibited rich cytoplasm, rough endoplasmic reticula and prominent and well- developed Golgi complexes. Transmission electron microscopy demonstrated the presence of lamellar bodies, which are cytoplasmic structures related to surfactant production, in FLSs from both sources. Increased levels of pinocytosis and numbers of pinocytotic vesicles were observed in RA-FLSs (p < 0.05). Basal production of MMP-3 and IL-6 was present in RA-FLSs and CIA-FLSs. Regarding the production of MMP-3 and IL-6 and the activation of signaling pathways, the present study demonstrated a lower response to IL-1β by CIA-FLSs than by RA-FLSs. Conclusion This study provides a comprehensive understanding of the biology of RA-FLS and CIA-FLS. The differences and similarities in ultrastructural morphology and important inflammatory cytokines shown, contribute to future in vitro studies using RA-FLS and CIA-FLS, in addition, they indicate that the adoption of CIA-FLS for studies should take careful and be well designed, since they do not completely resemble human diseases.

Effects of low-level laser on the expression of interleukin-6, tumor necrosis factor‑α, osteoprotegerin, and receptor activator of nuclear factor-κB ligand in human periodontal ligament cells / 华西口腔医学杂志

OBJECTIVES@#This study aims to determine the effects of low-level laser (LLL) on the expression of interleukin-6 (IL-6), tumor necrosis factor (TNF)-α, osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL) in human periodontal ligament cells (HPDLCs) stimulated by high glucose; and identify the molecular mechanism of LLL therapy in the regulation of periodontal inflammation and bone remodeling during orthodontic treatment in diabetic patients.@*METHODS@#HPDLCs were cultured in vitro to simulate orthodontic after loading and irradiated with LLL therapy. The cultured cells were randomly divided into four groups: low glucose Dulbecco's modification of Eagle's medium (DMEM)+stress stimulation (group A), high glucose DMEM+stress stimulation (group B), hypoglycemic DMEM+LLL therapy+stress stimulation (group C), and hyperglycemic DMEM+LLL therapy+stress stimulation (group D). Groups C and D were further divided into C1 and D1 (energy density: 3.75 J/cm2) and C2 and D2 (energy density: 5.625 J/cm2). Cells in groups A, B, C, and D were irradiated by LLL before irradiation. At 0, 12, 24, 48, and 72 h, the supernatants of the cell cultures were extracted at regular intervals, and the protein expression levels of IL-6, TNF-α, OPG, and RANKL were detected by enzyme-linked immunosorbent assay.@*RESULTS@#1) The levels of IL-6 and TNF-α secreted by HPDLCs increased gradually with time under static pressure stimulation. After 12 h, the levels of IL-6 and TNF-α secreted by HPDLCs in group A were significantly higher than those in groups B, C1, and C2 (P<0.05), which in group B were significantly higher than those in groups D1, and D2 (P<0.01). 2) The OPG protein concentration showed an upward trend before 24 h and a downward trend thereafter. The RANKL protein concentration increased, whereas the OPG/RANKL ratio decreased with time. Significant differen-ces in OPG, RANKL, and OPG/RANKL ratio were found among group A and groups B, C1, C2 as well as group B and groups D1, D2 (P<0.05).@*CONCLUSIONS@#1) In the high glucose+stress stimulation environment, the concentrations of IL-6 and TNF-α secreted by HPDLCs increased with time, the expression of OPG decreased, the expression of RANKL increased, and the ratio of OPG/RANKL decreased. As such, high glucose environment can promote bone resorption. After LLL therapy, the levels of IL-6 and TNF-α decreased, indicating that LLL therapy could antagonize the increase in the levels of inflammatory factors induced by high glucose environment and upregulate the expression of OPG in human HPDLCs, downregulation of RANKL expression in HPDLCs resulted in the upregulation of the ratio of OPG/RANKL and reversed the imbalance of bone metabolism induced by high glucose levels. 2) The decrease in inflammatory factors and the regulation of bone metabolism in HPDLCs were enhanced with increasing laser energy density within 3.75-5.625 J/cm2. Hence, the ability of LLL therapy to modulate bone remodeling increases with increasing dose.

Influence of matrine on Th17/Treg balance in rats with inflammatory bowel disease by regulating IL-6/STAT3/NF-κB signaling pathway / 西安交通大学学报(医学版)

【Objective】 To investigate the influence of matrine (MT) on the balance of T helper cell 17 (Th17)/regulatory T cells (Treg) in rats with inflammatory bowel disease by regulating interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3)/nuclear transcription factor-κB (NF-κB) pathway. 【Methods】 SD rats were grouped into control check group (CK group), model group, low-dose MT group (MT-L group, 50 mg/kg), medium-dose MT group (MT-M group, 100 mg/kg), high-dose MT group (MT-H group, 200 mg/kg), mesalazine group (MSLM group, 0.42 g/kg), and MT-H+rIL-6 (IL-6 activator) group (200 mg/kg+0.05 mg/kg) according to the random number table method, with 18 in each group. Except for the CK group, the rats in other groups all received with 5% trinitrobenzenesulfonic acid (20 mg/kg) buffer solution mixed with 50% ethanol at a ratio of 1∶1 and then enema to construct a rat model of inflammatory bowel disease. After the successful modeling, they were treated with drug administration once a day for 7 weeks. The body weight of rats was measured at 1, 3, 5, and 7 weeks of administration; the changes of colon length of rats in each group were compared; HE staining was used to detect the pathological damage of rat colon tissue; the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-17 and IL-10 in serum of rats were detected by ELISA; the proportions of Th17 and Treg cells in peripheral blood of rats were detected by flow cytometry; Western blottingt was performed to detect the protein expression of retinoic acid-related orphan receptor γt (RORγt), forkhead box protein P3 (Foxp3), IL-6, p-STAT3, and p-NF-κB p65 in rat colon tissue. 【Results】 Compared with the CK group, the colon tissue of the model group was severely damaged by pathology, and the body weight (at 3, 5, and 7 weeks), the level of IL-10, the proportion of Treg cell, and the expression of Foxp3 protein were decreased, the colon length shortened, the levels of TNF-α, IL-17, the proportions of Th17 cell, Th17/Treg ratio, and the protein expression of RORγt, IL-6, p-STAT3, and p-NF-κB p65 increased (P<0.05). Compared with the model group, the corresponding indicators of the MT-L group, MT-M group, MT-H group, and MSLM group had the opposite trends (P<0.05); rIL-6 attenuated the promoting effect of high-dose MT on Th17/Treg balance in inflammatory bowel disease rats. 【Conclusion】 MT may promote Th17/Treg balance in inflammatory bowel disease rats by inhibiting IL-6/STAT3/NF-κB signaling pathway.

Expression level and clinical significance of SOCS1 in the serum of patients with chronic HBV-related liver disease / 西安交通大学学报(医学版)

【Objective】 To study the expression levels of suppressor of cytokine signaling 1 (SOCS1) and its clinical significance in hepatitis B virus (HBV)-related liver diseases. 【Methods】 For this study we enrolled 25 patients with chronic hepatitis B (CHB), hepatitis B cirrhosis, or HBV-associated chronic acute liver failure (HBV-ACLF), and 25 healthy controls. The expression levels of SOCS1 mRNA in peripheral blood mononuclear cells (PBMCs) were determined using the RT-PCR method. The levels of SOCS1 and interleukin-6 (IL-6) in the plasma of patients with chronic liver diseases and healthy controls were measured using the ELISA method. The relative expression levels of SOCS1, SOCS1 mRNA, and other laboratory test indicators such as HBV-DNA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), prothrombin activity (PTA) and total bilirubin (TBil) were compared among the groups. Additionally, the correlation between the expression levels of SOCS1 mRNA and the aforementioned laboratory indicators was assessed. 【Results】 The expression levels of SOCS1 mRNA and serum SOCS1 were highest in the HBV-ACLF group, followed by the cirrhosis group, and lowest in the healthy control group, with statistically significant differences (F=109.65, P<0.001). The relative expression of SOCS1 mRNA was positively correlated with TBil (r=0.89, P<0.001), ALT (r=0.89, P<0.001), AST (r=0.84, P<0.001) and IL-6 (r=0.93, P<0.001), but negatively correlated with PTA (r=-0.89, P<0.001) and was not significantly correlated with HBV-DNA (P=0.28). 【Conclusion】 The expression levels of SOCS1 in patients with HBV-related chronic liver diseases can reflect the severity of the disease and show a significant correlation with indicators used to assess the severity of liver diseases.

Interleukin-6 in Skeletal Muscle Mass Regulation / 中国生物化学与分子生物学报

Interleukin-6 (IL-6) is a spreading pleiotropic cytokine, with both anti-inflammatory and proinflammatory effects. It not only participates in the body immune responses but also is involved in the biological regulative processes among different organs, tissues, and cells. IL-6 has both anti-inflammatory and pro-inflammatory effects. In the early stage of pathogen infection, IL-6 plays an anti-inflammatory role in the body, and its level is moderately increased in the body to resist inflammation and maintain internal homeostasis. However, a large amount of IL-6 release can cause excessive inflammation and trigger other pathological changes in the body. Il-6 also has the dual effect of stimulating the synthesis and degradation of skeletal muscle protein in regulating skeletal muscle mass. As an important locomotive organ, skeletal muscle is also one of the key targets of IL-6. IL-6 takes part in the biological control of skeletal muscle hypertrophy through regulating muscle satellite cell proliferation and differentiation under specific stresses. In addition IL-6 is also associated with skeletal muscle atrophy induced by aging and other pathological stresses. In addition, during exercise stress, skeletal muscle can also serve as an endocrine organ to secrete and release IL-6 that facilitates the "crosstalk" between skeletal muscle and other organs or tissues. As IL-6 plays as a versatile role in our body, this paper reviews the research progress of the mechanism of IL-6 in the regulation of skeletal muscle mass, which may provide theoretical support for revealing the molecular mechanism of skeletal muscle stresses and adaptations.

Erythrocyte membrane-associated protein inhibiting Th17 cell differentiation via IL-6 / STAT3 / ROR-γt signaling pathway in experimental autoimmune encephalomyelitis mice / 解剖学报

Objective To explore the effect of exogenous and endogenous erythrocyte membrane-associated protein (ERMAP) on helper T cell 17 (Th17) cell differentiation through interleukin 6 / signal transducers and activators of transcription 3 / retionoid-related orphan nuclear receptor-γt(IL-6 / STAT3 / ROR-γt) signal pathway in the mouse model of experimental autoimmune encephalomyelitis (EAE) . Methods Using flow cytometry to verify the function of ERMAP-Ig fusion protein at different concentrations; Agarose gel electrophoresis was performed to identify ERMAP knockout mice. Flow cytometry was performed to detect the effect of ERMAP-Ig fusion protein on Th17 cell differentiation in vitro. Forty 6-week-old normal C57BL / 6 mice were randomly divided into 2 groups to establish EAE models, control-Ig and ERMAP-Ig groups, with 20 mice in each group; Clinical scores were recorded; Flow cytometry was performed to detect Th17 cell differentiation in EAE mice in vivo. Forty 6-week-old identified wild-type and ERMAP knockout mice were divided into 2 groups to establish EAE models. Identified wild-type and ERMAP knockout mice were divided into 2 groups to establish EAE models, ERMAP

Effect of interleukin-6 on nucleated erythrocytes in lipopolysaccharide-induced preeclampsia rats / 解剖学报

Objective To explore the effect of interleukin (IL)-6 on nucleated erythrocytes in lipopolysaccharide (LPS)-induced preeclampsia rats. Methods ELISA and immunohistochemistry were used to detect the IL-6 in peripheral blood and placenta of preeclampsia and normal pregnancy; Flow cytometry and immunofluorescence were used to detect the maternal nucleated erythrocytes. Pregnant SD rats were randomly divided into 3 groups: the control, LPS and LPS +anti-IL-6 group; IL-6, the proportion of nucleated erythrocytes, JAK2/MEK and PI3K/Akt signal-related genes were detected. Results The IL-6 of preeclampsia was higher than that of normal patients. Compared with the Control group, IL-6, the proportion of nucleated erythrocytes and JAK2, P85, Akt, P65, IL-IB mRNA of LPS group increased, the fetal weight decreased; Compared with the LPS group, IL-6, the proportion of nucleated erythrocytes and JAK2, P85, Akt, P65 and IL-IB mRNA of the LPS + anti-IL-6 group decreased. Conclusion The up-regulation of IL-6 of preeclampsia patients is accompanied by increased nucleated erythrocytes in peripheral blood. Neutralizing IL-6 in vivo may down-regulate JAK2/ PI3K/Akt/NF-KB-signal-mediated IL-IB to protect preeclampsia rats.

Effect of gingival stem cells-derived exosomes on interlukin (IL)-6 and tumor necrosis factor (TNF)-α expression in rats with periodontitis / 预防医学

Objective @#To evaluate the effect of gingival stem cells-derived exosomes (GMSC-Exos) treatment on the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in rats with periodontitis, so as to provide the evidence for periodontitis treatment.@*Methods@#Forty specific pathogen-free (SPF) rats at ages of 8 weeks were randomly divided into 4 groups, including the blank group, periodontitis group, GMSC-Exos group and PBS group. Rats in the periodontitis group, GMSC-Exos group and PBS group were modeled for periodontitis using the ligature method. Rats in the blank group and periodontitis group were given no treatment, while rats in the GMSC-Exos group and PBS group were given 20 μL GMSC-Exos and PBS by injection, respectively. The periodontal index was measured in all rats 4 weeks post-treatment, and the TNF-α and IL-6 levels were measured in rat serum samples using enzyme-linked immunosorbent assay (ELISA). The TNF-α and IL-6 gene expression was quantified using the polymerase chain reaction (PCR) assay in the gingival tissues of the rat left upper maxillary area, and the periodontal tissues in the left upper maxillary areas were sampled for pathological examinations. Periodontal clinical indexes, IL-6 and TNF-α levels were compared in each group.@*Results@#The gingival sulcus bleeding index, gingival index, probing depth, and plaque index in the GMSC-Exos group (1.87±0.41, 1.03±0.19, 1.91±0.09 and 1.11±0.17) were higher than those in the blank group (0.96±0.31, 0.83±0.31, 1.09±0.05 and 1.01±0.38), but lower than those in the periodontitis group (2.65±0.50, 1.36±0.22, 2.61±0.07 and 1.51±0.26) and PBS group (2.44±0.50, 1.23±0.20, 2.49±0.10 and 1.39±0.28) (all P<0.05). The serum IL-6 and TNF-α levels in the GMSC-Exos group [(205.97±11.47) and (90.11±8.57) pg/mL] were higher than those in the blank group [(143.10±4.87) and (80.07±5.13) pg/mL], but lower than those in the periodontitis group [(367.33±13.89) and (158.29±13.10) pg/mL] and PBS group [(364.23±13.62) and (140.60±11.73) pg/mL] (all P<0.05). The IL-6 and TNF-α mRNA expression in the rat gingival tissues in the GMSC-Exos group (1.09±0.14 and 1.61±0.29) was higher than that in the blank group (0.99±0.10 and 1.06±0.14), but lower than that in the periodontitis group (1.63±0.09 and 3.63±0.26) and PBS group (1.58±0.11 and 3.79±0.32) (all P<0.05). Pathological examinations showed alleviation of periodontal tissue destruction, inflammatory cell infiltration and alveolar bone resorption, and no obvious root dental root regeneration in the junctional combined epithelium in the GMSC-Exos group relative to the periodontitis group and the PBS group. @*Conclusion@#Administration of GMSC-Exos may reduce periodontal inflammation and alveolar bone resorption by inhibiting IL-6 and TNF-α expression in rats with periodontitis.

Role of interleukin-6 in ocular inflammatory diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Interleukin-6(IL-6)is a pleiotropic cytokine produced by monocytes, macrophages, T lymphocytes and other cell types. It is significantly up-regulated in the process of infection and inflammation, and is the core cytokine of the host's defense against environmental stresses(such as injury and infection). Abnormal and persistent IL-6 production is closely associated with the development of various autoimmune and inflammatory diseases. A growing number of studies have shown that IL-6 plays a critical role in ocular inflammation and angiogenesis in the conjunctiva, cornea, uvea and retina. Blockade of IL-6 ameliorates chronic and refractory intraocular inflammation. This article aims to review the role as well as the mechanism of IL-6 in ocular inflammatory diseases, attempting to have a deep and systematic understanding of the role of IL-6 in ocular inflammatory diseases.

Detection of plasma interleukin-6, C-reactive protein, D-dimer and fibrinogen among 96 patients with pneumoconiosis / 预防医学

Objective@# To investigate the plasma levels of interleukin-6 (IL-6), C-reactive protein (CRP), D-dimer (D-D) and fibrinogen (Fib) among patients with pneumoconiosis, so as to provide insights into the prevention of thrombosis among patients with pneumoconiosis.@*Methods@#Ninety-six male coal workers with stable-stage pneumoconiosis admitted to China Pingmei Shenma Group Occupational Disease Prevention and Control Hospital from February 2019 to February 2021 were included in the pneumoconiosis group, and 43 male healthy volunteers in the hospital during the same period were selected as the control group. The plasma D-D, Fib, IL-6 and CRP levels were detected from subjects in the two groups. The associations of plasma D-D and Fib levels with IL-6 and CRP levels were examined using Pearson correlation analysis among pneumoconiosis patients. @*Results@#Participants in the pneumoconiosis group and the control group had a mean age of (52.91±3.89) and (52.64±4.12) years, D-D of (1.28±0.91) and (0.44±0.11) mg/L, Fib of (4.41±0.98) and (2.88±0.61) g/L, IL-6 of (0.63±0.19) and (0.42±0.06) ng/L and CRP of (3.30±1.65) and (1.35±0.12) mg/L, respectively. Higher plasma D-D, Fib, IL-6 and CRP levels were detected in the pneumoconiosis group than in the control group (all P<0.05). The plasma D-D level correlated positively with IL-6 level among pneumoconiosis patients (r=0.347, P<0.001). @*Conclusion@#High plasma IL-6, CRP, D-D and Fib levels are detected among patients with pneumoconiosis, and the plasma D-D level correlates positively with IL-6 level among patients with pneumoconiosis.

Research Progressin the Relationship between Interleukin-6 and Intervertebral Disc Degeneration / 中国医学科学院学报

Intervertebral disc degeneration (IDD) is one of the main diseases causing low back pain,which seriously affects the quality of life of patients.Recent studies have discovered that interleukin-6 (IL-6) is highly expressed in the tissues and cells of degenerative intervertebral disc and is closely related to the occurrence and development of IDD.However,the signaling pathway and role of IL-6 in IDD remain to be understood.Therefore,this article reviews the recent studies about the signaling pathway and role of IL-6 in IDD,aiming to facilitate the clinical work and subsequent research progress.