Detoxification II Prescription Suppresses the Th-17/IL-17 Inflammatory Axis to Improve the Liver Function of ACLF-Rats via Inactivating the P38MAPK Pathway

Hepatitis is a metabolic system disease which is a serious challenge to the medical and healthcare system of the world. This study attempted to investigate the therapeutic effect and illustrate the regulation pharmacological mechanism of Detoxification II Prescription on ACLF. In this study, the rats were injected with D-galactosamine to establish ACLF-rat models, and the levels of cholinesterase (CHE), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBiL) were measured with the related kits to reflect the liver functions of the rats. The levels of IL-17, IL-6, and IFN-γ in the serums of the rats were detected by qRT-PCR, and the percentages of Th-17 cells in CD4+ cells of the rats were measured by flow cytometry assay. In the results, the increased ALT, AST, TBiL, IL-6, IL-17, IFN-γ, and percentage of Th-17 cells in CD4+ and decreased ALB and CHE were found in the serums of the ACLF-rats, while Detoxification II Prescription could partly reverse those indexes of the ACLF-rats. Moreover, it was also found that Detoxification II Prescription could inhibit the expression of P38MAPK, and P38MAPK downregulation obviously improved the liver function indexes of the ACLF-rats including the levels of ALT, AST, TBiL, IL-6, IL-17, IFN-γ, and percentage of Th-17 cells in CD4+ cells. In conclusion, this study suggested that Detoxification II Prescription could suppress the Th-17/IL-17 inflammatory axis to improve the liver function of ACLF-rats via inhibiting the activity of the P38MAPK pathway.

Cardiometabolic Comorbidities in Patients With Psoriasis: Focusing on Risk, Biological Therapy, and Pathogenesis

Psoriasis is a chronic inflammatory disease characterized by erythematous scaly plaques, accompanied by systemic damage that leads to the development of multiple comorbidities. In particular, the association between psoriasis and cardiometabolic comorbidities, including cardiovascular diseases (CVDs), obesity, diabetes mellitus, and metabolic syndrome, has been verified in a considerable number of clinical trials. Moreover, the increased risk of cardiometabolic comorbidities positively correlates with psoriasis severity. Biologic therapy targeting inflammatory pathways or cytokines substantially improves the life quality of psoriasis patients and may affect cardiometabolic comorbidities by reducing their incidences. In this review, we focus on exploring the association between cardiometabolic comorbidities and psoriasis, and emphasize the benefits and precautions of biologic therapy in the management of psoriasis with cardiometabolic comorbidities. The pathogenic mechanisms of cardiometabolic comorbidities in psoriasis patients involve common genetic factors, lipid metabolism, insulin resistance, and shared inflammatory pathways such as tumor necrosis factor-α and interleukin-23/Th-17 pathways.

Lactate Is a Metabolic Mediator That Shapes Immune Cell Fate and Function

Lactate and the associated H+ ions are still introduced in many biochemistry and general biology textbooks and courses as a metabolic by-product within fast or oxygen-independent glycolysis. However, the role of lactate as a fuel source has been well-appreciated in the field of physiology, and the role of lactate as a metabolic feedback regulator and distinct signaling molecule is beginning to gain traction in the field of immunology. We now know that while lactate and the associated H+ ions are generally immunosuppressive negative regulators, there are cell, receptor, mediator, and microenvironment-specific effects that augment T helper (Th)17, macrophage (M)2, tumor-associated macrophage, and neutrophil functions. Moreover, we are beginning to uncover how lactate and H+ utilize different transporters and signaling cascades in various immune cell types. These immunomodulatory effects may have a substantial impact in cancer, sepsis, autoimmunity, wound healing, and other immunomodulatory conditions with elevated lactate levels. In this article, we summarize the known effects of lactate and H+ on immune cells to hypothesize potential explanations for the divergent inflammatory vs. anti-inflammatory effects.

Increased Numbers of Circulating Th22 and Th17 Cells in Children With Kawasaki Disease

T-helper (Th) 17 and Th22 cells are critical for the pathogenic process of Kawasaki Disease (KD). A total of 43 children with freshly diagnosed KD and 20 healthy controls (HC) were quantified for the numbers of Th17, Th22 and Th1 cells by flow cytometry. The concentrations of serum IL-17, IL-22, IL-6, IFN-γ and TNF-α were examined by ELISA. Compared to those in the HC, significantly increased numbers of Th17 and Th22 cells, but not Th1 cells, and higher levels of serum IL-17 and IL-22, but not IFN-γ, were found in KD patients. Stratification analysis indicated the numbers of both Th17 and Th22 cells and the concentrations of serum IL-17 and IL-22 in KD patients with coronary artery lesions (CAL) were significantly greater than that in those with noncoronary artery lesions (NCAL). Treatment with the intravenous immunoglobulin (IVIG) therapy significantly decreased numbers of Th22 and Th17 cells as well as the serum concentrations of IL-22 and IL-17 in KD patients. The concentrations of serum IL-22 and IL-17 were correlated positively with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values as well as N-terminal pro-brain natriuretic peptide (NT-proBNP) in those patients respectively. Conclusion: Our study provided direct evidence that Th22 and Th17 cells might contribute to the pathogenesis of KD.

Novel Presentation of Terminal Ileitis Associated with Secukinumab Therapy

Inflammatory bowel disease (IBD) and psoriasis are chronic inflammatory immune-mediated diseases. The interleukin-23- (IL23-) T helper (Th)17 pathway has been implicated in their pathogenesis, with multiple biologic therapies targeting this pathway. IL-17, the main proinflammatory cytokine produced by (TH)17, has been targeted by antibodies and IL-17 receptor blockers with favorable outcomes in treating psoriasis and psoriatic arthritis. However, their role in IBD is unpredictable as studies reported worsening of IBD with agents targeting IL-17 and rare case reports with new-onset IBD. We present a case of Crohn's-like severe terminal ileitis and worsening diverticulitis complicated by intestinal perforation requiring total parenteral nutrition shortly after being started on secukinumab.

Optimization of the dental implantation protocol in patients with partial secondary edentulousness and vitamin D deficiency

Relevance. The processes of osseointegration in the area of dental implant placement are accompanied by the development of reactions associ-ated with inflammation and activation of local immune processes in peri-implant tissues. Vitamin D preparations can have a significant local effect on the cells of the innate immune defense of the periodontal tissues.The aim of this work is to study the effectiveness of local application of vitamin D on the immune status of the peri-implant sulcus in rehabilitation of patients with partial secondary edentulous and chronic periodontitis by the method of dental implantation.Materials and methods. Determination of the content of biomarkers (IL-1RA, MCP-1, VEGF, TGF-β1, sTNFR) in the crevicular fluid before the installation of implants and the peri-implantation furrow fluid was carried out by the method of enzyme-linked immunosorbent assay using commercial kits «Vector Best» reagents after 3 and 6 months after surgery. The assessment of the state of the bone tissue was carried out using the Orthopantomograph tm OP300 apparatus (KAVO Dental, Germany). Vitamin D has been used topically at a therapeutic dosage.Results. Vitamin D, by reducing Th-1 and Th-17 cell proliferation and differentiation, blocks the activity of the immune-inflammatory process that occurs during implant placement.Conclusion. Application of colecalciferol in patients with moderate periodontitis leads to the activation of the production of immunoregulatory cyto-kines by the cellular structures of the peri-implantation furrow and can be used in combination with the traditional protocol in this category of patients.

Cytometric analysis of patients with COVID-19: what is changed in the second wave?

Background Coronavirus disease 2019 (COVID-19) pandemic had a 1st wave in Europe from March to May 2020 and a 2nd wave since September 2020. We previously studied 35 hospitalized COVID-19 patients of the 1st wave demonstrating a cytokine storm and the exhaustion of most lymphocyte subpopulations. Herein, we describe the results obtained from COVID-19 patients of the 2nd wave. Methods We analyzed interleukin (IL)-6 by human-specific enzyme-linked immunosorbent assay and a large set of lymphocyte subpopulations by flow cytometry in 274 COVID-19 patients hospitalized from September 2020 to May 2021. Results Patients of 2nd wave compared with those of 1st wave showed lower serum IL-6 levels and a higher number of B and most T lymphocyte subpopulations in advanced stages, in relation with the age and the gender. On the other hand, we observed in 2nd wave patients: (i) a reduction of most lymphocyte subpopulations at mild and moderate stages; (ii) a reduction of natural killer cells and T regulatory cells together with a higher number of activated T helper (TH) 17 lymphocytes in all stages, which were mainly related to steroid and azithromycin therapies before hospitalization. Conclusions COVID-19 had a less severe impact in patients of the 2nd wave in advanced stages, while the impact appeared more severe in patients of mild and moderate stages, as compared with 1st wave patients. This finding suggests that in COVID-19 patients with milder expression at diagnosis, steroid and azithromycin therapies appear to worsen the immune response against the virus. Furthermore, the cytometric profile may help to drive targeted therapies by monoclonal antibodies to modulate specific IL/lymphocyte inhibition or activation in COVID-19 patients.

Th17 Cells in Periodontitis and Its Regulation by A20

Periodontitis is a prevalent chronic disease that results in loss of periodontal ligament and bone resorption. Triggered by pathogens and prolonged inflammation, periodontitis is modulated by the immune system, especially pro-inflammatory cells, such as T helper (Th) 17 cells. Originated from CD4+ Th cells, Th17 cells play a central role for they drive and regulate periodontal inflammation. Cytokines secreted by Th17 cells are also major players in the pathogenesis of periodontitis. Given the importance of Th17 cells, modulators of Th17 cells are of great clinical potential and worth of discussion. This review aims to provide an overview of the current understanding of the effect of Th17 cells on periodontitis, as well as a brief discussion of current and potential therapies targeting Th17 cells. Lastly, we highlight this article by summarizing the causal relationship between A20 (encoded by TNFAIP3), an anti-inflammatory molecule, and Th17 cell differentiation.

Gut Microbiota Has a Crucial Role in the Development of Hypertension and Vascular Dysfunction in Toll-like Receptor 7-Driven Lupus Autoimmunity

Our group has investigated the involvement of gut microbiota in hypertension in a murine model of systemic lupus erythematosus induced by Toll-like receptor (TLR)-7 activation. Female BALB/c mice were randomly assigned to four experimental groups: an untreated control (CTR), a group treated with the TLR7 agonist imiquimod (IMQ), IMQ-treated with vancomycin, and IMQ-treated with a cocktail of broad-spectrum antibiotics. We carried out faecal microbiota transplant (FMT) from donor CTR or IMQ mice to recipient IMQ or CTR animals, respectively. Vancomycin inhibited the increase in blood pressure; improved kidney injury, endothelial function, and oxidative stress; and reduced T helper (Th)17 infiltration in aortas from IMQ-treated mice. The rise in blood pressure and vascular complications present in IMQ mice were also observed in the CTR mice recipients of IMQ microbiota. Reduced relative populations of Sutterella and Anaerovibrio were associated with high blood pressure in our animals, which were increased after stool transplantation of healthy microbiota to IMQ mice. The reduced endothelium-dependent vasodilator responses to acetylcholine induced by IMQ microbiota were normalized after interleukin-17 neutralization. In conclusion, gut microbiota plays a role in the TLR7-driven increase in Th17 cell, endothelial dysfunction, vascular inflammation, and hypertension. The vascular changes induced by IMQ microbiota were initiated by Th17 infiltrating the vasculature.