Methotrexate for refractory adult atopic dermatitis leads to alterations in cutaneous IL-31 and IL-31RA expression

Abstract Background: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). Objective: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. Methods: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-α, IFN-γ, TARC, and CCL-22. Results: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. Study limitations: Small sample size and limited length of follow-up. Conclusions: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA.

Cytokines in Oral Submucous Fibrosis: A Bird’s Eye View

Introduction: Oral Submucous Fibrosis (OSF) is a chronic fibrosis condition of oral cavity. It is a multifactorial condition, are- canut chewing being the prime etiologic factors. Objectives: Arecanut alkaloids stimulate the oral tissue initiating the inflammatory response. As an inflammatory response, cells release cytokines activating the cascade of different fibrinogenic pathways leading to fibrosis. Conclusion: This review briefs about the various cytokines studied in Oral Submucous Fibrosis.

Epithelial responses and Candida albicans pathogenicity are enhanced in the presence of oral streptococci

Abstract Experimental models that consider host-pathogen interactions are relevant for improving knowledge about oral candidiasis. The aim of this study was to assess the epithelial immune responses, Candida penetration of cell monolayers, and virulence during mixed species culture infections. Single species cultures of Candida albicans and mixed cultures (C. albicans, Streptococcus mutans, and Streptococcus sanguinis) were used to infect monolayers of HaCaT and FaDu ATCC HTB-43 cells for 12 h. After infection, IL-18 and IL-34 gene expression was measured to assess epithelial cell immune responses, and lactate dehydrogenase (LDH) activity was measured as an indicator of cell damage. Microscopy determined C. albicans morphology and penetration of fungal cells through the keratinocyte monolayer. Monolayers devoid of infection served as controls. Data were analyzed by an ANOVA one-way test followed by Tukey's post-hoc test (α = 0.05). The results found that IL-18 and IL-34 gene expression and LDH activity were significantly (p < 0.05) upregulated for both cell lines exposed to mixed species cultures compared with C. albicans alone. Candida albicans yeast and hyphae were evident in C. albicans only infections. In contrast, monolayers infected by C. albicans, S. mutans, and S. sanguinis exhibited higher microbial invasion with several hyphal aggregates detected. The presence of streptococci in C. albicans infection enhances the virulence and pathogenicity of the fungus with associated increased immune responses and tissue damage. Extrapolation of these findings to oral infection would indicate the added potential benefit of managing bacterial components of biofilms during treatment.

Resumo O objetivo deste estudo foi avaliar a resposta epithelial imune, a colonização da Candida albicans em monocamadas celulares e sua virulência em resposta a infecções de culturas de biofilme multiespécie. Culturas de biofilme monoespécie de C. albicans e culturas mistas (C. albicans, Streptococcus mutans e Streptococcus sanguinis) foram utilizadas para infectar monocamadas de células HaCaT e FaDu por 12 h. Após a infecção, a expressão dos genes IL-18 e IL-34 foi medida para avaliar as respostas imunes das células epiteliais. A atividade da lactato desidrogenase (LDH) foi medida como um indicador de dano celular. A microscopia determinou a morfologia de C. albicans e a penetração das células fúngicas através da monocamada de queratinócitos. Monocamadas em que não houve infecção serviram como controles. Os dados foram analisados por um teste ANOVA one-way seguido pelo teste post-hoc de Tukey (α = 0,05). Os resultados demonstraram que a expressão gênica de IL-18 e IL-34 e a atividade de LDH foram (p < 0,05) reguladas positivamente para ambas as linhagens de células expostas a culturas de espécies mistas em comparação com C. albicans isoladamente. Leveduras de C.albicans e hifas foram evidentes em infecções apenas por C. albicans. Entretanto, monocamadas infectadas por C. albicans, S. mutans e S. sanguinis exibiram maior invasão microbiana com vários agregados de hifas detectados. Dessa maneira, a presença de estreptococos na infecção por C. albicans aumentou a virulência e a patogenicidade do fungo com respostas imunes aumentadas associadas a danos nos tecidos. A extrapolação desses achados para a infecção oral indicaria o potencial benéfico do controle dos componentes bacterianos em biofilmes durante a terapia da candidíase

Effect of acute or subchronic stress on T cell response in peripheral blood: Regulatory role of vitamin D

The immune response, orchestrated by helper (Th1, Th2, and Th17) and regulatory (Treg) T cells, is modulated by stress and Vitamin D (Vit-D). Although the immunomodulatory functions of both are known, their specific roles on Th cells have not been fully clarified, yet. On this background, we aimed to investigate the effect of acute or subchronic stress on the distribution of peripheral T lymphocytes, as well as the immunomodulatory role of Vit-D. Young adult male, Swiss-albino mice (30–40g) were allocated to the control, acute stress (AS), subchronic stress (ChS), control+Vit-D, AS+Vit-D, and ChS+Vit-D groups (n=11/group). The combined cold (2-h at 4°C)-immobilization (2-h in a restrainer) stress protocol was employed as one day in AS groups and five consecutive days in ChS groups. Vit-D (2?g/kg ip) was applied every other day, until the end of the protocol. Serum cortisol, Vit-D and cytokine levels (IL-4, IFN-?, and IL-17A) were measured, and lymphocytes from blood samples were subtyped by flow-cytometry. Stress exposure caused differential Th and Treg responses, acute stress shifting the response to Th1, and subchronic stress shifting the response to Th2. Th17 and Treg cells were lower in subchronic stress exposed mice. These changes became comparable to control values in Vit-D treated groups. The T cell response, crucial for immune system function, differs on the basis of stress exposure as such the Vit-D treatment. The tolerogenic profile created by Vit-D should be considered for management of stress-related diseases. Our results may help to provide a better understanding of disease pathogenesis.

Effects of acupuncture and moxibustion on histamine and inflammatory factors in the skin tissue at Tianshu (ST25) of rats with Crohn disease / 针灸推拿医学（英文版）

Objective: To explore the potential mechanism of acupuncture and moxibustion in treating Crohn disease (CD) by evaluating the changes in histamine and inflammatory factors in the skin tissue at Tianshu (ST25) of rats.Methods: Fifty-eight Sprague-Dawley rats were randomly divided into a normal group (n=14) and a CD-modeling group (n=44). Rats in the CD-modeling group received enema with 2,4,6-trinitrobenzene sulfonic acid plus ethanol to establish CD models. The enema was repeated once every 7 d for a total of 4 times. After modeling, four modeled rats and four normal rats were randomly selected for model identification. After the CD model was successfully established, the remaining rats in the CD-modeling group were randomly divided into a model group, an acupuncture group, a moxibustion group, and a Western medication group, with ten rats in each group. The rats in the acupuncture and moxibustion groups were treated with acupuncture or moxibustion at Tianshu (ST25) and Shangjuxu (ST37); the rats in the Western medication group were treated with mesalazine enteric-coated tablets by gavage for continuous 7 d. After the intervention, the colon tissue of rats in each group was collected. After gross observation, hematoxylin-eosin (HE) staining was performed to further observe the pathological changes. The expression of histamine in the skin tissue at Tianshu (ST25) was detected by enzyme-linked immunosorbent assay. The expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-18, IL-10, and IL-6 in the skin tissue at Tianshu (ST25) was detected by Western blotting. Results: Compared with the normal group, the colonic wall of rats in the model group showed cobblestone-like changes, local ulcers, and polyps in dark red and thickening and hardening. HE staining showed local loss of mucosal epithelial layer and formation of slit-like ulcers, destruction of mucosal glands, edema, and infiltration of inflammatory cells in lamina propria and submucosa, and occasional formation of sarcoid-like granuloma. The levels of histamine and IL-6 were significantly up-regulated (P<0.01, P<0.05), and the levels of TNF-α, IL-18, and IL-10 were significantly down- regulated (P<0.01 or P<0.05) in the skin tissue at Tianshu (ST25) of rats in the model group. Compared with the model group, the pathomorphological damage of the colon tissue of rats in the acupuncture group, moxibustion group, and Western medication group was significantly improved. The levels of histamine and IL-6 were significantly down- regulated (P<0.01, P<0.05), and the level of IL-10 was significantly up-regulated (P<0.01) in the skin at Tianshu (ST25) of rats in the acupuncture group. The levels of histamine and IL-6 were significantly down-regulated (P<0.01, P<0.05), and the levels of TNF-α, IL-18, and IL-10 were significantly up-regulated (P<0.01 or P<0.05) in the skin tissue at Tianshu (ST25) of rats in the moxibustion group. The level of histamine was significantly down-regulated (P<0.01), and the levels of IL-18 and IL-10 were significantly up-regulated (P<0.05, P<0.01) in the skin tissue of rats in the Western medication group. Compared with the acupuncture group, the level of IL-10 in the skin tissue at Tianshu (ST25) of rats in the moxibustion group was significantly up-regulated (P<0.01). Conclusion: The inflammatory responses in the skin tissue at Tianshu (ST25) may be the external manifestation of CD. Significant differences in the regulation of inflammatory responses in the skin tissue at Tianshu (ST25) between acupuncture and moxibustion exist, which may be caused by the differences in the stimulation characteristics between acupuncture and moxibustion.

Changes of high mobility group protein B1 in condyloma acuminatum and its clinical significance / 中国医师进修杂志

Objective:To investigate the changes and clinical significance of high mobility group protein B1 (HMGB1) in condyloma acuminatum (CA).Methods:Sixty four patients with initial CA(initial group) and 48 patients with recurrent CA(recurrent goup) treated in the Second Affiliated Hospital of PLA Air Force Military Medical University Hospital from January 2019 to November 2020 were included. In the same period, 31 patients who underwent circumcision and 19 female underwent sexual organ cosmetic plastic surgery were taken as the control group, and the normal foreskin and healthy vulva were collected. The expression of HMGB1 in wart was detected by real-time quantitative polymerase chain reaction(RT-PCR), and the expression of soluble apoptosis related factor ligand (sFasL), cell lymphoma-2 gene (Bcl-2), soluble apoptosis related factor (SFAS) and Survivin, caspase-3 were detected. At the same time, serum interleukin (IL) - 6, IL-17, IL-23 and tumor necrosis factor - α (TNF- α) were detected by enzyme-linked immunosorbent assay(ELISA).Results:The expression of HMGB1 mRNA in the warts of patients in the initial group, recurrence group and control group were 1.96 ± 0.20, 1.53 ± 0.14, 1.05 ± 0.11, there was statistical difference ( F = 15.20, P<0.05) ; the expression of HMGB1 mRNA in the warts of patients in the initial group was significantly higher than that in the recurrence group and the control group ( P<0.05), and the recurrence group was also significantly higher than that in the control group ( P<0.05). The mRNA expressions of sFas, Bcl-2, sFasL and caspase-3 in the warts of patients in the initial group were significantly lower than those in the recurrence group and the control group: 0.52 ± 0.08 vs. 0.82 ± 0.16, 1.10 ± 0.19; 0.50 ± 0.05 vs. 0.79 ± 0.13, 1.08 ± 0.21; 0.47 ± 0.06 vs. 0.81 ± 0.15, 1.01 ± 0.19; 0.35 ± 0.04 vs. 0.68 ± 0.09, 0.91 ± 0.16, P<0.05; and the recurrence group were also significantly lower than those in the control group ( P<0.05). The expression of Survivin mRNA in the warts of patients in the initial group was significantly higher than those in the recurrence group and the control group: 2.14 ± 0.40 vs. 1.60 ± 0.27, 0.99 ± 0.18, P<0.05, and the recurrence group was also significantly higher than that in the control group ( P<0.05). The serum levels of TNF-α and IL-6 in the initial group were significantly lower than that in the recurrence group and the control group: (20.08 ± 1.95) μg/L vs. (26.93 ± 2.74), (37.65 ± 3.83) μg/L; (31.05 ± 3.24) μg/L vs. (38.13 ± 3.76), (45.98 ± 4.69) μg/L, P<0.05; and the recurrence group were also significantly lower than those in the control group ( P<0.05). The serum levels of IL-17 and IL-23 in the primary group were significantly higher than those in the recurrence group and the control group: (423.71 ± 28.68) ng/L vs. (384.26 ± 21.70) and (335.43 ± 19.65) ng/L; (289.50 ± 18.53) ng/L vs. (251.07 ± 15.96) and (214.67 ± 13.20) ng/L, P<0.05; and the recurrence group were also significantly higher than those in the control group ( P<0.05). The results of correlation analysis showed that the mRNA expression of HMGB1 in the warts of CA patients were negatively correlated with the mRNA expression of caspase-3, sFas, Bcl-2 and sFasL in the warts ( r = - 0.602, - 0.734, - 0.692, - 0.717, P<0.05), and was positive correlation with Survivin mRNA expression ( r = 0.645, P<0.05); and were positive correlation with the contents of IL-17 and IL-23 in serum ( r = 0.673, 0.685, P<0.05), and negatively correlated with the contents of TNF-α and IL-6 ( r = - 0.698, - 0.764, P<0.05). Conclusions:HMGB1 is obviously abnormal in the warts of patients with condyloma acuminatum, and is closely related to apoptosis, immune and inflammation-related factors, and may be jointly involved in the occurrence and recurrence of CA.

Insights on the role of cytokines in carious lesions / Insights sobre o papel das citocinas em lesões cariosas

Objetivo: A resposta imune da dentina-polpa à patogênese da cárie ainda é pouco compreendida devido à complexa interação dos processos envolvidos. O objetivo desta revisão foi explorar o papel das citocinas e sua relevância na patogênese da cárie dental. Resultados: A cárie dentária pode resultar em uma resposta inflamatória do hospedeiro na polpa dental, caracterizada pelo acúmulo de células inflamatórias levando à liberação de citocinas inflamatórias como, Interleucina-4 (IL-4), Interleucina (IL-6), Interleucina-8 (IL-8) e fator de necrose tumoral­α(TNF-α). IL-4 parece estar correlacionada com a profundidade das lesões cariosas; IL-6 está fortemente correlacionada com a doença cárie e é considerada um potente biomarcador; IL-8 pode ser um potente biomarcador tanto para cárie quanto para outras alterações presentes na polpa e sua liberação está correlacionada com TNF-α e IL-6; TNF-α desempenha um papel importante não apenas na progressão da cárie, mas também em outros processos patológicos. Conclusao: Mediadores específicos têm um grande potencial para servir como biomarcadores quanto à presença e progressão da doença cárie, o que incita a necessidade de mais investigações nesse campo (AU).

Objectives: The dentin-pulp immune response to caries pathogenesis is still poorly understood due to the complex interplay of the involving processes. The aim of this review was to explore the role of cytokines and its relevance in the pathogenesis of dental caries. Results: Dental caries can result in a host inflammatory response in the dental pulp, characterized by the accumulation of inflammatory cells leading to the release of inflammatory cytokines such as Interleukin-4 (IL-4), Interleukin (IL-6), Interleukin-8 (IL-8) and Tumor necrosis factor­ α (TNF- α ). IL-4 seems to be correlated to the depth of carious lesions; IL-6 is strongly correlated to caries disease and is considered a potent biomarker; IL-8 can be a potent biomarker for both caries and other changes present in the pulp and, its release is correlated to TNF- α and IL-6; TNF-α plays an important role not only in caries progression, but also in other pathological processes. Conclusion: Specific mediators have a great potential to serve as biomarkers alluding to the presence and progress of caries disease, urging further investigations in the field (AU)

Highlights of clinical and laboratory parameters among severe COVID-19 patients treated with tocilizumab: a retrospective observational study

ABSTRACT BACKGROUND: Coronavirus disease 2019 (COVID-19) can cause cytokine release syndrome (CRS), which leads to high mortality rates. Tocilizumab suppresses CRS by blocking the signal transduction of interleukin-6 (IL-6). OBJECTIVE: To evaluate the clinical and laboratory parameters associated with mortality among patients receiving tocilizumab treatment. DESIGN AND SETTING: Retrospective observational study conducted in the chest disease departments of two different training and research hospitals in the center of Ankara, Turkey. METHODS: Patients who were hospitalized and treated with tocilizumab in September 2020 were retrospectively analyzed. Their laboratory parameters and clinical characteristics were obtained from the hospital information system database. Comparative analyses were performed between the patients who died and the ones who survived. RESULTS: A total of 58 patients who received tocilizumab treatment were included in this study, among whom 35 (60.3%) died. There was no difference between the mortality and survival groups in terms of white blood cell (WBC), neutrophil, lymphocyte, ferritin or C-reactive protein (CRP) levels detected on admission. WBC, lymphocyte, neutrophil and CRP levels measured on the third and fifth days after tocilizumab administration were found to be significantly lower in the survival group (P < 0.05). In multiple logistic regression analysis, age and oxygen saturation were determined to be independent risk factors for mortality. CONCLUSION: Persistently high WBC, CRP and neutrophil levels and low lymphocyte levels could be considered to be valuable indicators of mortality among COVID-19 patients treated with tocilizumab. Age and low oxygen saturation are independent risk factors for mortality among patients receiving tocilizumab treatment.

Inflammatory cytokines and alcohol use disorder: systematic review and meta-analysis

Objective: To assess differences in blood inflammatory cytokines between people with alcohol use disorder (AUD) and healthy controls (HC). Methods: Searches were performed from inception through April 14, 2021. Meta-analyses with random-effects models were used to calculate the standardized mean difference ([SMD], 95%CI), and potential sources of heterogeneity were explored trough meta-regressions and subgroup analysis. Results: The meta-analysis included 23 studies on the following 14 cytokines: tumor necrosis factor (TNF)-α, IL-1, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, IL15, interferon (IFN)-γ and sCD14. There were significantly higher concentrations of IL-6 (n=462 AUD and 408 HC; SMD = 0.523; 95%CI 0.136-0.909; p = 0.008) in AUD than HC. No significant differences were found in the other 13 cytokines. Conclusion: We found that IL-6 levels were significantly higher in individuals with AUD than HC and that other cytokines were not altered. This can be explained by the small number of studies, their methodological heterogeneity, and confounding factors (active use, abstinence, quantity, and physical or psychiatric illnesses, for example). Despite a great deal of evidence about alcohol and inflammatory diseases, studies assessing the role of neuroimmune signaling in the development and severity of AUD are still lacking.

Stem cell therapy as a potential treatment option for psoriasis

Abstract Psoriasis is a chronic inflammatory dermatological disorder characterized by white scales and clearly demarcated erythematous plaques. The prevalence of psoriasis varies from country to country and can occur at any age, implying that ethnicity, environmental factors, and genetic background all play a role in its onset. According to the World Psoriasis Day Consortium, 125 million people globally and 2%-3% of the overall community have psoriasis. The introduction of biological treatments has revolutionized the treatment of moderate to severe psoriasis. These novel drugs, particularly those targeting interleukin (IL)-17 and IL-23p19, can help most patients with psoriasis achieve clear or virtually clear skin with satisfactory durability. Nevertheless, none of these modern treatments are not entirely remedial in their current form, and alarmingly, a limited but growing proportion of patients with severe psoriasis are not responding satisfactorily to currently available treatments. Stem cell therapy, including regulatory T-cells, hematopoietic stem cell transplantation, and mesenchymal stromal cells, has been used in patients with recalcitrant psoriasis. This review discusses the stem cell treatments available for psoriasis.

Diagnostic value of different interleukins and procalcitonin in critically ill patients admitted with suspected sepsis

Background: Many biomarkers have now been studied such as C-reactive Protein (CRP), procalcitonin (PCT), etc., and are widely used for the diagnosis of sepsis in clinical practice which may determine the appropriate antibiotic treatment. A flowcytometric cytokine bead array (CBA) assay has now been used to determine multiple interleukins (IL), simultaneously. The aim of this study was to determine the cytokine (IL2, IL4, IL6, IL10, TNF?, INF?, and IL17) profiles of interleukins in plasma of sepsis patients by using multiplex Flowcytometric CBA array assay. Materials and Methods: A total of 99 consecutive patients admitted with the suspected sepsis were studied. PCT concentrations were measured by using the enzyme-linked fluorescent immunoassay (ELFA) technique and flow cytometry-based BD™ CBA Cytokine Kit was used to evaluate levels of 7 cytokines [IL-2, IL-4, IL-6, IL-10, Tumour Necrosis Factor (TNF), Interferon- ? (IFN-?), and IL-17A]. Results: Microbiologically defined infection (MDI) demonstrated a positive culture report in 79/99 (79.7%) of patients. The IL6 [1873.7 (4-5000)] and IL10 [(154.7 (0-1764)] levels were significantly higher in septic patients than those in the negative MDI IL6 [901 (4-5000)] and IL10 [110.4 (4-1372)] levels. The AUROC value of IL6 [0.66 (0.53-0.79)] was found to be the highest among all followed by IL10 [0.65 (0.51-0.79)], IFN? [0.63 (0.51-0.77)], PCT [0.61 (0.48-0.75)], and TNF? [0.55 (0.42-0.69)]. Conclusion: Our study suggests that that IL6 is substantially more economical and can reduce the investigation cost to half as compared with the procalcitonin assay.

Detection of foot-and-mouth disease virus type O in recovered as well as healthy cattle to study carrier status in Assam

Foot and mouth disease (FMD), one of the most contagious diseases of animals, affects different host species including wild animals. Asymptomatic FMD recovered animals may remain as carrier, which may be threat to other healthy animals. Hence, it is necessary to monitor the carrier status of the FMD recovered animals to effectively prevent further spread of the disease. Out of all the seven serotypes of FMD, O serotype is most commonly found in livestock. Therefore, in the present study, we chose to detect serotype ‘O’ in oropharyngeal fluid (OP) and to quantify cytokines, viz. IL-1?, IL-1? and IL-2. A total of 30 OP fluids and 30 blood samples were collected from 10 animals (1 in-contact healthy animal) for 3 months post infection. FMD O serotype could be detected in all the animals (100%). The RQ values were found to be 0.014 to 63.118 and 0.162 to 46.889 for IL-1? and IL-1? genes respectively, while insignificant RQ values were obtained for IL-2. In the second and third months, two animals showed down regulation for IL-1? gene, while IL-1? and IL-2 genes were down regulated in 7 animals and in all 10 animals, respectively for all the three months.

Association of level of IL-6, IL-10, IL-18, tumour necrosis factor-?with rheumatic mitral stenosis and subsequent pulmonary hypertension

Background:Objective of the study was to provide insight on the immune response in patients of rheumatic heart disease, mitral stenosis and evaluation of various cytokines in pulmonary hypertension secondary to rheumatic heart disease.Methods:Total 163 subjects, more than 18 year of age, were enrolled in this study. 84 subjects with rheumatic mitral stenosis (group A) diagnosed on two-dimensional echocardiography (2D echo)and 79 normal healthy volunteers(group B). Patients with mitral stenosis were further divided into subgroups based on severity of mitral stenosis [mitral valve area (MVA >1 cm2 and MVA <1 cm2)(subgroup Aa and Ab)]and presence or absence of pulmonary hypertension [pulmonary arterial systolic pressure (PASP >36 mm Hg)(subgroup Ac and Ad)]. Interleukins IL-6, IL-10, IL-18, tumour necrosis factor alpha (TNF-?)andhigh-sensitivity C-reactive protein (hs-CRP)levels were assessed in both groups.Results:Mean IL-6, IL-10, IL-18, TNF-? and hs-CRP in group A and group B was 6.57�53 and 2.73�p?0.001), 8.185�8 and 3.51�86(p?0.001), 136.31�.0 and 47.96�76(p?0.001), 21.26�.59 and 5.36�57(p?0.001), 4.69�3 and 2.63�22(p?0.008) respectively. On subgroup analysis mean TNF-? in subgroup Aa was 20.71�.84, while in subgroup Ab was 7.56�93 (p?0.001). Mean IL-10 in subgroup Ac and Ad was 8.74�29 and 7.47�82, respectively. Differences in levels of other cytokines in these subgroups were not found statistically significant.Conclusions:This study finds increased IL-6, IL-10, IL-18, TNF-? and hs-CRP levels in subjects with rheumatic mitral stenosis. Subjects with severe mitral stenosis had increased TNF-? levels. Subjects of mitral stenosis having pulmonary hypertension had increased IL-10 levels.

INSULIN RESISTANCE ALTER THE LEVELS OF IL-4, IL-5 AND IL-13 IN TYPE 2 DIABETES MELLITUS WITH LESS THAN 5 YEARS OF DURATION

The harmonious biochemical processes in a healthy individual are due to the balance between essential molecules that are necessary for the maintenance of physiology of the living system. These include energy bio-molecules, co-factors for oxidation to attain energy expenditure, regulatory hormones, and protective immune system. Objectives: Identifying predictive factors for 2DM will be beneficial to developing effective prevention and early detection of the disease. Therefore, the novelty of this study is to evaluate whether infiammatory markers are different in individuals with versus without T2DM. To assess the effect of glucose, insulin, Homeostasis metabolic assessment-estimated insulin resistance (HOMA-IR), lipids on cytokine variables in type 2DM subjects. Materials& Methods: Two hundred and thirty individuals are recruited in to this present study after the approval from Institutional ethical committee for the present study. The study was conducted in the Department of Biochemistry, Malwanchal university, Indore, India. Age & sex matched one hundred and fifteen human non-2DM individuals were taken into healthy control group. One hundred and fifteen subjects, on treatment for 2DM were included in second group.Results: On comparison of age, Tc, and Ldl parameters between 2DM and control group subjects showed insignificant differences, whereas parameters of FBS (t=12.24; df=228; P<0.001) HbA1c (t=16.40; df=228; P<0.05) and insulin mean levels (t=2.70; df=228; P<0.05) showed a significant difference. Decrease in the levels of serum IL-4 was observed in 2DM subjects when compared with healthy control subjects. On the contrary, we observed increase in the values of IL-5 and IL-13 in 2DM subjects when compared with healthy control subjects. In case of IL-10 and IL-12 values, we observed no significance when compared between the group subjects. Conclusion: The present study concludes that there is association of IL-4, IL-5 and IL-13 with relation to 2DM. These cytokines can be used as biomarkers for early identification and diagnosis of secondary complications in 2DM individuals

Efficacy of Kechuanning combined with western medicine in the treatment of phlegm-heat obstructing lung syndrome AECOPD and its effects on inflammatory factors / 中国基层医药

Objective:To investigate the efficacy of Kechuanning combined with western medicine on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and its effects on serum amyloid A, interleukin 1β and procalcitonin levels. Methods:A total of 104 patients with AECOPD who received treatment in Yongkang Hospital of Traditional Chinese Medicine from January 2019 to December 2020 were included in this study. They were randomly assigned to receive either symptomatic treatment with western medicine alone ( n = 52, control group) or symptomatic treatment with western medicine combined with Kechuanning ( n = 52, observation group). Therapeutic effects, latency to clinical symptom relief, pre- and post-treatment pulmonary function, serum inflammatory factor levels, and blood gas analysis indexes were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [86.54% (45/52) vs. 67.31%(35/52), χ2 = 4.99, P < 0.05]. Latency to rale disappearance, latency to cough disappearance, length of hospital stay in the observation group were (8.25 ± 1.38) days, (10.05 ± 1.53) days, and (12.65 ± 2.28) days, which were significantly shorter than those in the control group [(9.41 ± 1.46) days, (12.19 ± 1.61) days, (14.36 ± 2.14) days, t = 4.16, 6.98, 3.61, all P < 0.05]. After treatment, forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1), and FEV 1/FVC value in the observation group were (1.88 ± 0.5) L, (64.13 ± 5.72)%pred, (59.43 ± 5.57)%, respectively, which were significantly higher than those in the control group [(1.65 ± 0.51) L, (60.22 ± 5.60)% pred, (54.16 ± 5.19)%, t = 2.17, 3.52, 4.99, all P < 0.05]. Arterial partial pressure of oxygen (PaO 2) and blood oxygen saturation (SpO 2) in the observation group were (9.18 ± 0.89) kPa and (96.26 ± 2.13)%, respectively, which were significantly higher than those in the control group [(8.74 ± 0.76) kPa, (94.07 ± 2.08)%, t = 2.71, 5.305, both P < 0.05]. Partial pressure of carbon dioxide (PaCO 2) in the observation group was significantly lower than that in the control group [(7.32 ± 0.27) kPa vs. (7.63 ± 0.32) kPa, t = 5.34, P < 0.05]. Serum amyloid protein, interleukin-1β and procalcitonin levels in the observation group were (43.84 ± 6.15) mg/L, (3.24 ± 0.51) μg/L, (1.55 ± 0.37) ng/L, respectively, which were significantly lower than those in the control group [(55.26 ± 3.46) mg/L, (4.19 ± 0.56) μg/L, (2.03 ± 0.46) ng/L, t = 9.23, 9.04, 5.86, all P < 0.05]. Conclusion:Kechuanning as an adjuvant therapy for AECOPD can greatly improve lung function and hypoxia, alleviate clinical symptoms, reduce inflammatory reactions, and have a definite clinical effect. The study is innovative and scientific and is worthy of clinical reference.

Role of epithelium-derived cytokines interleukin-33, interleukin-25 and thymic stromal lymphopoietin in the pathogenesis of atopic dermatitis / 中华皮肤科杂志

Epidermal barrier defects and immune abnormalities are the main pathophysiological changes in the development of atopic dermatitis (AD) . Skin keratinocytes can release a variety of inflammatory factors and mediators under the treatment with various harmful factors. Three epithelium-derived cytokines interleukin (IL) -33, IL-25 and thymic stromal lymphopoietin are considered to be effective inducers of Th2 immune response in skin or mucosal barrier, which can activate immune cells, cause the secretion of Th2 cytokines, enhance the Th2 immune response, and participate in the occurrence and development of AD. This review focuses on the role of the above 3 epithelium-derived cytokines in the pathogenesis of AD.

Expression of peripheral interleukin-35 and its modulatory effect on regulatory T cell functions in patients with alopecia areata / 中华皮肤科杂志

Objective:To investigate changes in the peripheral interleukin-35 (IL-35) level in patients with alopecia areata, and to assess its modulatory effect on regulatory T (Treg) cell activities.Methods:Totally, 81 patients with alopecia areata (alopecia areata group) and 27 healthy volunteers (control group) were enrolled from Shanxi Provincial People′s Hospital between December 2019 and January 2021. Sera and peripheral blood mononuclear cells (PBMCs) were isolated. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the serum IL-35 level, real-time fluorescence-based quantitative PCR to determine the mRNA expression of IL-35 subunits EBI3 and IL-12p35, and flow cytometry to determine the proportion of CD4 + CD25 + CD127 dim/- Treg cells. Sorted Treg cells were stimulated by recombinant human IL-35, ELISA was performed to detect levels of perforin and granzyme B in the culture supernatant, and real-time fluorescence-based quantitative PCR to determine the mRNA expression of EBI3, IL-12p35, and immune checkpoint molecules, such as programmed death protein 1 (PD-1) , T cell immunoglobulin and mucin protein-3 (Tim-3) , cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and lymphocyte activation gene-3 (LAG-3) in Treg cells. IL-35-stimulated or unstimulated Treg cells were co-cultured with autologous PBMCs, and cell counting kit-8 (CCK8) assay was conducted to assess cellular proliferative activity. Measurement data were compared between 2 groups by using t test, comparisons among multiple groups were carried out by using one-way analysis of variance, correlation analysis was carried out by using Pearson correlation analysis, and enumeration data were compared by using chi-square test. Results:Compared with the control group, the alopecia areata group showed significantly decreased IL-35 levels (90.10 ± 11.98 ng/L vs. 100.74 ± 28.71 ng/L, t= 2.71, P= 0.008) , mRNA expression of EBI3 and IL-12p35 in PBMCs (EBI3: 1.06 ± 0.15 vs. 1.25 ± 0.11, t= 6.09, P < 0.001; IL-12p35: 1.00 ± 0.15 vs. 1.38 ± 0.22, t= 10.16, P < 0.001) , and proportions of Treg cells (5.91% ± 1.17% vs. 6.85% ± 1.23%, t= 3.54, P= 0.001) . In the alopecia areata group, the proportion of Treg cells was positively correlated with the serum IL-35 level ( r= 0.25, P= 0.026) , and the mRNA expression of EBI3 and IL-12p35 in PBMCs ( r= 0.31, 0.24, P= 0.004, 0.032, respectively) . Compared with the control group, the unstimulated Treg cells from the alopecia areata group showed significantly decreased supernatant levels of perforin and granzyme B, mRNA expression of EBI3, IL-12p35 and immune checkpoint molecules ( P < 0.05 or 0.001) , as well as weakened inhibitory effect on the proliferative activity of PBMCs ( P= 0.013) . There was no significant difference in the level of perforin or granzyme B between the recombinant human IL-35-stimulated and unstimulated Treg cells from the patients with alopecia areata (both P > 0.05) . However, the mRNA expression of EBI3, IL-12p35 and immune checkpoint molecules was significantly higher in the IL-35-stimulated Treg cells than in the unstimulated Treg cells in the alopecia areata group ( P < 0.05 or 0.001) , and the inhibitory effect on the proliferative activity of PBMCs was also significantly enhanced in the IL-35-stimulated Treg cells compared with the unstimulated Treg cells ( P= 0.037) . Conclusion:The peripheral IL-35 level was significantly decreased in the patients with alopecia areata, which was closely associated with reduced activities of Treg cells, and IL-35 may be involved in the occurrence of alopecia areata.

Biological agents in the treatment of moderate to severe plaque psoriasis and psoriatic arthritis / 中华皮肤科杂志

Psoriasis is an immune-mediated chronic recurrent inflammatory disease, and biological agents targeting cytokines and their receptors involved in its pathogenesis have become an increasingly important option for its treatment in recent years. With the successive appearance of biological agents such as secukinumab and ustekinumab on the market in China, the use of biologics will become increasingly common in the treatment of psoriasis. This review summarizes the efficacy of different biological agents and individualized drug selection in the treatment of moderate to severe plaque psoriasis and psoriatic arthritis, with a view to providing a reference for physicians in clinical practice.

IL-6 and IL-10 gene polymorphisms and susceptibility to autoimmune thyroid disease: a Meta analysis / 中华地方病学杂志

Objective:To clarify the relationship between interleukin (IL)-6, IL-10 gene polymorphisms and autoimmune thyroid disease (AITD).Methods:Literature search was conducted through databases such as PubMed, Web of Science, CNKI, Embase, Wanfang Database and VIP.com, and domestic and foreign literatures related to IL-6, IL-10 gene polymorphisms and AITD were included in the study. The time limit was from the self-built of the databases to July 2021. Meta-analysis was performed with STATA 16.0 software, the odds ratio ( OR) and 95% confidence interval ( CI) were used as effect indicators, random-effect or fixed-effect model was selected according to the heterogeneity results, and the source of heterogeneity was explored through subgroup analysis. Publication bias was assessed using funnel plots and Egger's test. Results:Finally, 19 literatures were included, all in English. There were 12 studies on IL-6 genes and 11 studies on IL-10 genes, including 4 studies on both IL-6 and IL-10 genes. In the whole population, the loci associated with AITD were IL-6 -174 G/C site (GG vs CC + GC: OR =1.94, 95% CI = 1.01 - 3.76), IL-6 -572 G/C site (GG + GC vs CC: OR = 0.49, 95% CI = 0.29 - 0.84; GG vs CC + GC: OR = 0.76, 95% CI = 0.60 - 0.96; GG + CC vs GC: OR = 0.63, 95% CI = 0.49 - 0.81), IL-10 -819 T/C site (TT + TC vs CC: OR = 1.84, 95% CI = 1.01 - 3.34; T vs C: OR = 1.59, 95% CI = 1.00 - 2.51), and IL-10 -1 082 A/G site (AA + AG vs GG: OR = 0.77, 95% CI = 0.64 - 0.92; AA vs GG + AG: OR = 2.03, 95% CI = 1.16 - 3.58; A vs G: OR = 0.76, 95% CI = 0.61 - 0.94). The results of subgroup analysis showed that in Asian population, the loci associated with AITD were IL-6 -174 G/C site (GG vs CC + GC: OR = 4.61, 95% CI = 1.11 - 19.23; G vs C: OR = 0.65, 95% CI = 0.44 - 0.97); IL-6 -572 G/C site (GG vs CC + GC: OR = 0.64, 95% CI = 0.41 - 0.99; GG + CC vs GC: OR = 0.60, 95% CI = 0.38 - 0.94); IL-10 -819 T/C site (TT + TC vs CC: OR = 2.51, 95% CI = 1.48 - 4.25; T vs C: OR = 1.91, 95% CI = 1.05 - 3.46); and IL-10 -1 082 A/G site (AA + AG vs GG: OR = 0.66, 95% CI = 0.52 - 0.84; AA vs GG + AG: OR = 2.83, 95% CI = 1.54 - 5.21; A vs G: OR = 0.66, 95% CI = 0.53 - 0.82). Conclusion:IL-6 -174 G/C, IL-6 -572 G/C, IL-10 -819 T/C and IL-10 -1 082 A/G polymorphisms are associated with the susceptibility to AITD, especially in Asians.

Interleukin and perihematomal edema after intracerebral hemorrhage / 国际脑血管病杂志

In different stages of the course of intracerebral hemorrhage, various interleukins (ILs) play different roles. IL-1α and IL-1β can aggravate perihematomal edema (PHE) by affecting the integrity of the blood-brain barrier in the early stage of intracerebral hemorrhage. IL-6 and IL-8 play a key role in the whole course of intracerebral hemorrhage and affect the severity of PHE by inducing inflammation. IL-3 promotes the development of PHE by promoting microglia activation. IL-11 and IL-17A can be used to assess disease severity and as predictors of PHE, but they do not play a decisive role in the development of intracerebral hemorrhage. IL-4 and IL-10 have certain improvement effects on the development of PHE and the outcomes after cerebral hemorrhage.