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2.
Rev. Soc. Bras. Med. Trop ; 54: e0744-2020, 2021. tab, graf
Article in English | LILACS | ID: biblio-1155546

ABSTRACT

Abstract INTRODUCTION Suckling by schistosomotic mice improves anti-ovalbumin (OA) antibody production, while delayed-type hypersensitivity (DTH) remains unaffected. This property of milk from schistosomotic mice was investigated in IL-12/IL-23-deficient mice (IL-12p40KO). METHODS We compared anti-OA DTH, IgG2a and cytokines in wild-type and IL-12p40KO mice suckled by infected (SIM) or non-infected (CONTROL) mothers. RESULTS SIM mice showed similar intensity and eosinophils in the DTH, which was abolished in IL-12p40KO and IL-12p40KO-SIM mice. In IL-12p40KO-SIM, IgG2a and TGF-β levels were higher, but IL-6 levels were lower. CONCLUSIONS Milk from schistosomotic mothers may evoke IgG2a without eliciting DTH in IL-12/IL-23 deficiencies, by changing TGF-β/IL-6 levels.


Subject(s)
Humans , Animals , Female , Schistosoma mansoni , Interleukin-12 , Immunoglobulin G , Transforming Growth Factor beta , Interleukin-23 , Mice , Mothers
3.
Chinese Acupuncture & Moxibustion ; (12): 1023-1028, 2021.
Article in Chinese | WPRIM | ID: wpr-921003

ABSTRACT

OBJECTIVE@#To observe the effect of electroacupuncture (EA) on expression of interleukin (IL) -23/IL-17 axis and Toll-like receptor 4 (TLR4) in the infarcted tissue in rats with myocardial infarction (MI), and to explore the mechanism of EA on alleviating MI injury.@*METHODS@#Forty male SD rats were randomly divided into a sham-operation group, a sham-operation plus EA group, a model group and an EA group, 10 rats in each group. The MI models were established by ligation of left anterior descending coronary artery in the model group and EA group, while only threading was performed in the sham-operation group and sham-operation plus EA group. The rats in the sham-operation plus EA group and EA group were treated with EA at "Neiguan" (PC 6), disperse-dense wave, 2 Hz/100 Hz, 2 mA, once a day, 20 min each time, for 3 days. After the intervention, the ejection fraction (EF) was measured by echocardiography to evaluate the cardiac function; the infarct area was measured by TTC staining; the HE staining was used to observe the morphological changes of myocardial tissue; the levels of IL-23 and IL-17 in infarcted tissue were detected by ELISA; the protein expression of TLR4 in infarcted tissue was detected by Western blot.@*RESULTS@#Compared with the sham-operation group, the EF was decreased (@*CONCLUSION@#EA may alleviate the excessive inflammatory response after MI by inhibiting the expression of IL-23/IL-17 axis in MI rats, and TLR4 may be involved during the process.


Subject(s)
Animals , Electroacupuncture , Interleukin-17/genetics , Interleukin-23/genetics , Male , Myocardial Infarction/therapy , Rats , Rats, Sprague-Dawley , Toll-Like Receptor 4/genetics
4.
J. appl. oral sci ; 28: e20190490, 2020. tab, graf
Article in English | LILACS, BBO | ID: biblio-1090781

ABSTRACT

Abstract The relationship between periodontitis and the pathogenesis of other inflammatory diseases, such as diabetes, rheumatoid arthritis and obesity has been an important topic of study in recent decades. The Th17 pathway plays a significant role in how local inflammation can influence systemic inflammation in the absence of systemic pathology. Objective: To determine Th17 biased-cells in systemically healthy patients in the presence of generalized chronic periodontitis. Methodology: A total of 28 patients were recruited without systemic inflammatory pathology, which was determined by clinical history, the Health Assessment Questionnaire (HAQ) and rheumatoid factor detection. Of these patients, 13 were diagnosed as healthy/gingivitis (H/G) and 15 as generalized chronic periodontitis (GCP). Th17 (CD4+CD161+) cells and Th17IL23R+ (CD4+CD161+IL-23R+) cells were quantified by flow cytometry, based on the total cells and on the lymphocyte region, termed the "enriched population" (50,000 events for each). Results: The percentages of Th17 cells of the H/G and periodontitis groups were similar on total cells and enriched population (19 vs 21.8; p=4.134 and 19.6 vs 21.8; p=0.55). However, Th17IL23R+ cells differ significantly between periodontally healthy patients and generalized chronic periodontitis patients in both total cell (0.22% vs 0.65%; p=0.0004) and enriched populations (0.2% vs 0.75%; p=0.0266). Conclusions: GCP patients (otherwise systemically healthy) were characterized by increased Th17-proinflammatory cell phenotype positive for the IL-23 receptor in peripheral blood. The proportion of Th17 cells that are negative for the IL-23 receptor in the peripheral blood of systemically healthy patients seemed to be unaffected by the presence or absence of chronic periodontitis.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Chronic Periodontitis/immunology , Th17 Cells/immunology , Phenotype , Case-Control Studies , Periodontal Index , Surveys and Questionnaires , Receptors, Interleukin/blood , Statistics, Nonparametric , Interleukin-23/blood , Chronic Periodontitis/pathology , Th17 Cells/pathology , Flow Cytometry , Gingivitis/immunology , Gingivitis/pathology
5.
An. bras. dermatol ; 94(6): 677-683, Nov.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1054900

ABSTRACT

Abstract Background: Psoriasis is a skin-articular disease with unclear etiopathogenesis. It has been suggested that the disease is immune-mediated by T-lymphocytes, predominantly Th17 cells. Similar to psoriasis, geographic tongue is an inflammatory disease with participation of Th17 cells and direct correlation with psoriasis. Objective: To investigate and compare the inflammatory responses and the Th17 pathway in psoriasis and geographic tongue. Methods: This was a cross-sectional study with 46 participants that were categorized into three groups: (A) patients with psoriasis vulgaris; (B) patients with geographic tongue and psoriasis; (C) patients with geographic tongue without psoriasis. All patients underwent physical examination, and a skin and oral biopsy for histopathological examination and immunohistochemical analysis with anti-IL6, anti-IL17, and anti-IL23 antibodies. Results: Histological analysis of all lesions showed mononuclear inflammatory infiltrate. However, moderate intensity was prevalent for the patients with geographic tongue and psoriasis and geographic tongue groups. Immunopositivity for the antibodies anti-IL6, anti-IL17, and anti-IL23 revealed cytoplasmic staining, mainly basal and parabasal, in both psoriasis and geographic tongue. Regarding IL-6, in patients with geographic tongue and psoriasis cases the staining was stronger than in patients with geographic tongue without psoriasis cases. IL-17 evidenced more pronounced and extensive staining when compared to the other analyzed interleukins. IL-23 presented similar immunopositivity for both geographic tongue and psoriasis, demonstrating that the neutrophils recruited into the epithelium were stained. Study limitation: This study was limited by the number of cases. Conclusion: The inflammatory process and immunostaining of IL-6, IL-17, and IL-23 were similar in geographic tongue and psoriasis, suggesting the existence of a type of geographic tongue that represents an oral manifestation of psoriasis.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Psoriasis/pathology , Th17 Cells/pathology , Glossitis, Benign Migratory/pathology , Psoriasis/immunology , Biopsy , Severity of Illness Index , Immunohistochemistry , Keratinocytes/pathology , Cross-Sectional Studies , Interleukin-6/immunology , Interleukin-17/immunology , Interleukin-23/immunology , Th17 Cells/immunology , Glossitis, Benign Migratory/immunology , Antibodies/analysis
6.
Yonsei Medical Journal ; : 713-719, 2019.
Article in English | WPRIM | ID: wpr-762115

ABSTRACT

PURPOSE: We aimed to evaluate the clinical significance of a disintegrin and metalloproteinase 8 (ADAM 8) as a potential blood biomarker for gastric cancer (GC). MATERIALS AND METHODS: Blood ADAM 8 was measured by ELISA. Cytokines/chemokines [interleukin-23 (IL-23), stromal cell-derived factor 1α/CXC chemokine ligand 12 (SDF-1α/CXCL12), interleukin-8 (IL-8), and soluble CD40 ligand (sCD40L)] were measured by chemiluminescent immunoassay. They were compared among five groups; normal/gastritis, high-risk, early GC (EGC), advanced GC (AGC) without distant metastasis, and AGC with distant metastasis by one-way analysis of variance in both training (n=80) and validation dataset (n=241). Clinicopathological features of GC and GC-associated cytokines were evaluated for their correlations with blood ADAM 8. To evaluate the diagnostic accuracy to predict GC, receiver operating characteristic (ROC) curve and logistic regression were used. RESULTS: Blood ADAM 8 significantly increased along GC carcinogenesis in both training (ANOVA, p<0.001) and validation dataset (p<0.001). It was significantly higher in EGC compared to high-risk (post-hoc Bonferroni, p=0.041) and normal (p<0.001). It was also higher in AGC compared with high-risk (p<0.001) and normal (p<0.001) groups. However, no significant difference was found between cancer groups. Blood ADAM 8 was correlated with N-stage (Spearman's correlation, γs=0.320, p=0.011), but not with T-stage or M-stage. Pearson's correlations showed blood ADAM 8 was closely correlated with pre-inflammatory cytokines, IL-23 (p=0.036) and SDF-1α/CXCL12 (p=0.037); however, it was not correlated with pro-angiogenic cytokine IL-8 (p=0.313), and sCD40L (p=0.702). ROC curve and logistic regression demonstrated that blood ADAM 8 showed higher diagnostic accuracy (sensitivity, 73.7%; specificity, 86.2%) than CEA (sensitivity, 23.1%; specificity, 91.4%). Combination of ADAM 8 and CEA further increased the diagnostic accuracy to predict GC (sensitivity, 81.8%; specificity, 84.0%). CONCLUSION: Blood ADAM 8 is a promising biomarker for early detection of GC.


Subject(s)
Carcinogenesis , CD40 Ligand , Cytokines , Dataset , Early Diagnosis , Enzyme-Linked Immunosorbent Assay , Immunoassay , Interleukin-23 , Interleukin-8 , Logistic Models , Neoplasm Metastasis , ROC Curve , Sensitivity and Specificity , Stomach Neoplasms
7.
Article in Korean | WPRIM | ID: wpr-766569

ABSTRACT

Psoriasis is a chronic inflammatory disease. Medical therapy is the mainstay of the management of psoriasis, and the main target of psoriasis treatment is immunological dysregulation. Cyclosporine and methotrexate, the main conventional psoriasis treatments, usually lead to a Psoriasis Area and Severity Index (PASI) 75 response in 50% to 60% of patients, but show some organ toxicity. Biologics for psoriasis have recently become the main therapeutic agents for moderate to severe psoriasis unresponsive to conventional treatment. Tumor necrosis factor-α inhibitors were the first anti-psoriatic biologics to be developed, and also show good efficacy for psoriatic arthritis. Ustekinumab, the sole biologic designed for the inhibition of interleukin (IL)-12/23, has been most widely used for psoriasis in Korea. The main strength of ustekinumab is its relatively long treatment interval. IL-17 inhibitors have recently been introduced in Korea for psoriasis treatment. Secukinumab and ixekizumab are currently available IL-17 inhibitors that block the development of psoriasis lesions in the downstream events of psoriasis pathogenesis. They have excellent therapeutic efficacy, with a PASI 90 response in up to 60%–70% of patients. Selective IL-23 inhibitors have been more recently introduced in our country. They have an excellent PASI 90 response, and a longer injection interval than IL-17 inhibitors. New immunological modulators such as phosphodiesterase inhibitors, tyrosine kinase 2 inhibitors, and janus kinase inhibitors are planned to be introduced for psoriasis treatment. These are small molecules that can be administered orally, and some patients who are reluctant to receive injection therapy are expected to favor these therapeutic agents.


Subject(s)
Arthritis, Psoriatic , Biological Products , Cyclosporine , Humans , Interleukin-17 , Interleukin-23 , Interleukins , Korea , Methotrexate , Necrosis , Phosphodiesterase Inhibitors , Phosphotransferases , Psoriasis , Severity of Illness Index , Tumor Necrosis Factor-alpha , TYK2 Kinase , Ustekinumab
8.
Article in English | WPRIM | ID: wpr-739401

ABSTRACT

PURPOSE: Endotype in chronic rhinosinusitis (CRS) has been established in the last decade. However, the exact immunologic profile of CRS still has controversy because it has a considerable immunologic heterogeneity. Therefore, we investigated various inflammatory mediators according to different nasal tissues in chronic rhinosinusitis and compared them within the same subject. METHODS: We collected uncinate process mucosa (UP) and nasal polyp (NP) tissues from controls, CRS without NP (CRSsNP) and CRS with NP (CRSwNP). Expression levels of 28 inflammatory mediators including T helper (Th) 1, Th2, Th17, proinflammatory cytokines and remodeling markers were determined by multiplex immunoassay and were analyzed using paired tests as well as principal component analysis (PCA) to investigate endotype in each subtype of CRS. RESULTS: Signature inflammatory mediators are interleukin (IL)-5, C-C motif chemokine ligand (CCL)-24, monocyte chemoattractant protein (MCP)-4, and vascular cell adhesion molecule (VCAM)-1 in eosinophilic NP, whereas IL-17A, IL-1β, and matrix metallopeptidase (MMP)-9 were detected as signature inflammatory markers in non-eosinophilic NP. Despite differences in inflammatory cytokine profile between eosinophilic and non-eosinophilic NP, the common upregulation of IL-5, CCL-11, IL-23, IL-2Rα, VCAM-1, MMP-3 and MMP-9 were shown in NP compared to UP within the same subject. In the PCA, we observed that Th2 immune response was helpful in discriminating between nasal tissues in subtypes of CRS and that there was a partial overlap between non-eosinophilic NP and eosinophilic NP in terms of Th2 mediators. CONCLUSIONS: Commonly upregulated mediators in NP were Th2-associated, compared with UP regardless of CRS subtypes, whereas signature markers were distinct in each NP subtype. These findings imply that Th2 inflammatory responses may play a role in the development of NP regardless of CRSwNP subtypes.


Subject(s)
Cytokines , Eosinophils , Immunoassay , Interleukin-17 , Interleukin-23 , Interleukin-5 , Interleukins , Monocytes , Mucous Membrane , Nasal Polyps , Passive Cutaneous Anaphylaxis , Population Characteristics , Principal Component Analysis , Rhinitis , Sinusitis , Up-Regulation , Vascular Cell Adhesion Molecule-1
9.
Article in Chinese | WPRIM | ID: wpr-771501

ABSTRACT

To observe the clinical curative effect of Qingying Tang in the treatment of psoriatic blood-heat syndrome and explore its intrinsic mechanism.In this study,we collected 72 patients with blood-heat syndrome psoriasis admitted to our dermatology clinic from January 2016 to December 2017 and divided into control group and observation group according to the random number table method,36 cases in each group.The patients in control group were given with Acitretin Capsules orally,10 mg/time,twice a day.The patients in observation group were given with Qingying Tang orally,150 mL/time,twice a day.The treatment period was 12 weeks in both groups.The traditional Chinese medicine(TCM) syndrome scores before and after treatment,psoriasis area and severity index(PASI) score,dermatology life quality index(DLQI) score,and the clinical efficacy of the two groups were compared between the two groups;flow cytometry was used to detect peripheral blood Th17 cell percentages before and after treatment in both groups;serum interleukin(IL)-17,IL-23,IL-22,and IL-21 levels in both groups before and after treatment were measured by ELISA;the expression levels of STAT3 and RORγt before and after treatment in patients were measured by using skin lesion immunohistochemical method.The results showed that the TCM symptoms were improved significantly in both groups(P<0.05),and the effect in observation group was significantly better than that in the control group(P<0.05).PASI and DLQI scores were decreased significantly after treatment in both groups(P<0.05),and the scores in observation group were significantly lower than those in the control group(P<0.05).The curative effect of the observation group was significantly higher than that of the control group(P<0.05).After treatment,the percentage of Th17 cells,as well as IL-17,IL-23,IL-22 and IL-21 levels in peripheral blood were significantly decreased in both groups(P<0.05),and the levels in observation group were significantly lower than those in the control group(P<0.05).The expression levels of STAT3 and RORγt in both groups were significantly lower than those before treatment(P<0.01),and the levels in observation group were significantly lower than those in the control group(P<0.05).All of the results indicted that Qingying Tang can effectively improve the skin lesions and TCM syndrome in patients with psoriasis and blood-heat syndrome,and improve patient health quality,which may be related to regulation of peripheral blood IL-23/Th17.


Subject(s)
Administration, Oral , Drugs, Chinese Herbal , Therapeutic Uses , Humans , Interleukin-23 , Allergy and Immunology , Psoriasis , Drug Therapy , Th17 Cells , Allergy and Immunology , Treatment Outcome
10.
Protein & Cell ; (12): 1027-1038, 2018.
Article in English | WPRIM | ID: wpr-757986

ABSTRACT

Macrophages acquire distinct phenotypes during tissue stress and inflammatory responses. Macrophages are roughly categorized into two different subsets named inflammatory M1 and anti-inflammatory M2 macrophages. We herein identified a unique pathogenic macrophage subpopulation driven by IL-23 with a distinct gene expression profile including defined types of cytokines. The freshly isolated resting mouse peritoneal macrophages were stimulated with different cytokines in vitro, the expression of cytokines and chemokines were detected by microarray, real-time PCR, ELISA and multiple colors flow cytometry. Adoptive transfer of macrophages and imiquimod-induced psoriasis mice were used. In contrast to M1- and M2-polarized macrophages, IL-23-treated macrophages produce large amounts of IL-17A, IL-22 and IFN-γ. Biochemical and molecular studies showed that IL-23 induces IL-17A expression in macrophages through the signal transducer and activator of transcription 3 (STAT3)-retinoid related orphan receptor-γ T (RORγT) pathway. T-bet mediates the IFN-γ production in IL-23-treated macrophages. Importantly, IL-23-treated macrophages significantly promote the dermatitis pathogenesis in a psoriasis-like mouse model. IL-23-treated resting macrophages express a distinctive gene expression prolife compared with M1 and M2 macrophages. The identification of IL-23-induced macrophage polarization may help us to understand the contribution of macrophage subpopulation in Th17-cytokines-related pathogenesis.


Subject(s)
Animals , Cell Polarity , Imiquimod , Interleukin-23 , Metabolism , Macrophages , Metabolism , Pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Psoriasis , Metabolism , Pathology
11.
Immune Network ; : e8-2018.
Article in English | WPRIM | ID: wpr-740203

ABSTRACT

Cytokines play a pivotal role in maintaining bone homeostasis. Osteoclasts (OCs), the sole bone resorbing cells, are regulated by numerous cytokines. Macrophage colony-stimulating factor and receptor activator of NF-κB ligand play a central role in OC differentiation, which is also termed osteoclastogenesis. Osteoclastogenic cytokines, including tumor necrosis factor-α, IL-1, IL-6, IL-7, IL-8, IL-11, IL-15, IL-17, IL-23, and IL-34, promote OC differentiation, whereas anti-osteoclastogenic cytokines, including interferon (IFN)-α, IFN-β, IFN-γ, IL-3, IL-4, IL-10, IL-12, IL-27, and IL-33, downregulate OC differentiation. Therefore, dynamic regulation of osteoclastogenic and anti-osteoclastogenic cytokines is important in maintaining the balance between bone-resorbing OCs and bone-forming osteoblasts (OBs), which eventually affects bone integrity. This review outlines the osteoclastogenic and anti-osteoclastogenic properties of cytokines with regard to osteoimmunology, and summarizes our current understanding of the roles these cytokines play in osteoclastogenesis.


Subject(s)
Cytokines , Homeostasis , Interferons , Interleukin-1 , Interleukin-10 , Interleukin-11 , Interleukin-12 , Interleukin-15 , Interleukin-17 , Interleukin-23 , Interleukin-27 , Interleukin-3 , Interleukin-33 , Interleukin-4 , Interleukin-6 , Interleukin-7 , Interleukin-8 , Macrophage Colony-Stimulating Factor , Necrosis , Osteoblasts , Osteoclasts , RANK Ligand
12.
Article in English | WPRIM | ID: wpr-718395

ABSTRACT

BACKGROUND: We aimed to investigate mucosal immunity related to forkhead box P3 (FOXP3+) regulatory T (Treg) cells, T helper 17 (Th17) cells and cytokines in pediatric inflammatory bowel disease (IBD). METHODS: Mucosal tissues from terminal ileum and colon and serum samples were collected from twelve children with IBD and seven control children. Immunohistochemical staining was done using anti-human FOXP3 and anti-RORγt antibodies. Serum levels of cytokines were analyzed using a multiplex assay covering interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-17A/F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, interferon (IFN)-γ, soluble CD40L, and tumor necrosis factor-α. RESULTS: FOXP3+ Treg cells in the lamina propria (LP) of terminal ileum of patients with Crohn's disease were significantly (P < 0.05) higher than those in the healthy controls. RORγt+ T cells of terminal ileum tended to be higher in Crohn's disease than those in the control. In the multiplex assay, serum concentrations (pg/mL) of IL-4 (9.6 ± 1.5 vs. 12.7 ± 3.0), IL-21 (14.9 ± 1.5 vs. 26.4 ± 9.1), IL-33 (14.3 ± 0.9 vs. 19.1 ± 5.3), and IFN-γ (15.2 ± 5.9 vs. 50.2 ± 42.4) were significantly lower in Crohn's disease than those in the control group. However, serum concentration of IL-6 (119.1 ± 79.6 vs. 52.9 ± 39.1) was higher in Crohn's disease than that in the control. Serum concentrations of IL-17A (64.2 ± 17.2 vs. 28.3 ± 10.0) and IL-22 (37.5 ± 8.8 vs. 27.2 ± 3.7) were significantly higher in ulcerative colitis than those in Crohn's disease. CONCLUSION: Mucosal immunity analysis showed increased FOXP3+ T reg cells in the LP with Crohn's disease while Th17 cell polarizing and signature cytokines were decreased in the serum samples of Crohn's disease but increased in ulcerative colitis.


Subject(s)
Antibodies , CD40 Ligand , Child , Colitis, Ulcerative , Colon , Crohn Disease , Cytokines , Humans , Ileum , Immunity, Mucosal , Inflammatory Bowel Diseases , Interferons , Interleukin-10 , Interleukin-17 , Interleukin-23 , Interleukin-33 , Interleukin-4 , Interleukin-6 , Interleukins , Mucous Membrane , Necrosis , T-Lymphocytes , T-Lymphocytes, Regulatory , Th17 Cells
13.
Article in Korean | WPRIM | ID: wpr-718274

ABSTRACT

Biologics are the most advanced treatment for psoriasis. Ustekinumab, one of the biologics for psoriasis, is a human monoclonal antibody that binds to the p40 subunit of interleukin-12 and interleukin-23. A 41-year-old woman with a 17-year history of plaque psoriasis and psoriatic arthritis presented with worsening lesions. The patient had previously been treated with a number of topical and systemic medications and narrow band ultraviolet B. However, none of the treatments consistently controlled her disease. Thus, treatment with ustekinumab 45 mg via subcutaneous injection was initiated. Approximately 7 days after the first treatment, she experienced a flare with generalized pustules in her whole body. The condition was controlled with systemic steroid treatment. The patient was subsequently treated with adalimumab, and improvement in her plaque and pustular lesions was noted. Herein, we report a case of psoriasis that flared up after ustekinumab therapy, which was accompanied by a morphological change from plaque to pustular lesions.


Subject(s)
Adalimumab , Adult , Arthritis, Psoriatic , Biological Products , Female , Glycogen Storage Disease Type VI , Humans , Injections, Subcutaneous , Interleukin-12 , Interleukin-23 , Psoriasis , Ustekinumab
14.
Article in Korean | WPRIM | ID: wpr-742127

ABSTRACT

The treatment of inflammatory bowel disease has evolved with the development of anti-TNF agents. In spite of long-term effectiveness, many patients do not respond or no longer responds to these drugs. Therefore, the development of new drugs that act on different inflammatory pathways has become necessary. Vedolizumab, a gut-specific biological agent, inhibits interaction α4β7 integrin with mucosal addressin cell adhesion molecule-1 without inhibiting systemic immune responses. Long-term vedolizumab therapy in patients with Crohn's disease and ulcerative colitis was safe and effective. Additionally, vedolizumab can be used in patients already failed an anti-TNF therapy. Ustekinumab is a fully human immunoglobulin G1 kappa monoclonal antibody that blocks the p40 subunit of IL-12 and IL-23. Ustekinumab will be a clinically effective agent to use in medically-refractory Crohn's disease especially as a second line drug. Tofacitinib is an oral, small molecule that inhibits JAK1, JAK3 and in a lesser extent, JAK2. Perhaps the most attractive things of these JAK inhibitors is that they are given orally instead of parenterally. Early results showed that patients with moderately to severely active ulcerative colitis receiving tofacitinib were more likely to achieve remission at 8 weeks than those receiving placebo. However, these results have not been as robust in Crohn's disease. Much of the positioning will depend on the safety profile such as opportunistic infection and atherogenic risk. The challenges for the future are to determine the therapeutic drug monitoring-guided dose optimization, optimal timing and drug combinations to produce the most effective, and safest outcomes for IBD patients.


Subject(s)
Cell Adhesion , Colitis, Ulcerative , Crohn Disease , Drug Combinations , Humans , Immunoglobulins , Inflammatory Bowel Diseases , Interleukin-12 , Interleukin-23 , Opportunistic Infections , Ustekinumab
15.
Pakistan Journal of Pharmaceutical Sciences. 2017; 30 (3 [Special]): 1139-1142
in English | IMEMR | ID: emr-189326

ABSTRACT

The effect of citrate to Desloratadine Citrate Disodium set in the treatment of chronic urticaria in patients with IL4, IL18, and IL23, IL33 levels was investigated. 100 cases of chronic urticaria treated in our hospital from January 2013 to January 2015 were divided into study group and control group by random number table method. Patients in the study group with chloric thunder of citric acid treatment, the control group were treated with mizolastine in the treatment, the treatment time for 2 weeks. The difference of curative effect between the two groups and the changes of IL4, IL18, IL23, IL 33 before and after treatment in two groups were compared. After two weeks of treatment, the total effective rate of the study group was 94%, while the total effective rate of the control group was only 78%, which was statistically significant [P<0.05]. Before treatment, the two groups of patients with IL4, IL18, IL23, IL33 levels were higher, and the difference between the groups was not statistically significant [P>0.05], after treatment, the two groups of patients with IL4, IL18, IL23, IL33 were decreased, but the study group patients decreased significantly, the data between the two groups was statistically significant [P<0.05]


Conclusion: Desloratadine citrate disodium treatment effect of chronic urticaria is better, and after treatment, IL4, IL18, IL23, IL33 levels decreased significantly


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Urticaria/drug therapy , Chronic Disease , Interleukin-4 , Interleukin-18 , Interleukin-23 , Interleukin-33
16.
PAFMJ-Pakistan Armed Forces Medical Journal. 2017; 67 (3): 483-487
in English | IMEMR | ID: emr-188583

ABSTRACT

Rheumatoid arthritis [RA] is an autoimmune disorder characterized by inflammation of synovium, cartilage damage and co-occurring of various other disorders. Significant improvement has been achieved in RA therapeutics in last two decades. However, newer, more efficient and more cost-effective therapeutic applications are still needed to be developed. Current therapies in RA are mostly acting to restrict inflammation. Non steroidal anti inflammatory drugs [NSAIDs] and disease modifying antirheumatic drugs [DMARDs] are conventionally used in RA therapy. Studies showed higher efficacy of anticyfokine therapy such as anti-IL-6 and anti-TNF. Rituximab, targeting B cells, after establishing its potential was approved to be used in combination with methotrexate in 2006. Abatacept, CLTA-4-IgGl, has been developed to block CD28 and CD80 or CD86 interaction leading to the termination T cell activation. Molecular inhibitors are relatively new in RA therapeutics such as tocilizumab, tofacitinib and baricitinib. PDA has approved tofacitinib to be used as a treatment for moderate and severe RA. Future holds promising therapeutic options based on numerous studies. IL-12, IL-17 and IL-23 are the targets of future anticytokine therapies. Several lymphocyte targeting agents including ofatumumab, ocrelizumab and veltuzumab have been developed and are currently in phase II and phase III clinical trials. There is a vast range of potential targets in RA enabling us to expand the therapeutic options over the next decade


Subject(s)
Humans , Autoimmune Diseases , Rituximab/therapeutic use , Methotrexate , Anti-Inflammatory Agents, Non-Steroidal , Interleukin-23 , Clinical Trials as Topic
17.
Braz. j. med. biol. res ; 50(11): e6527, 2017. graf
Article in English | LILACS | ID: biblio-888953

ABSTRACT

Immunological mechanisms have been proposed to underlie the pathogenesis of recurrent spontaneous abortion (RSA). Vitamin D has a potent immunomodulatory effect, which may affect pregnancy outcome. The objective of this study was to investigate 25-hydroxyvitamin D [25(OH) D] concentration and vitamin D receptor (VDR) expression in the decidual tissues of RSA patients. Thirty women with RSA (RSA group) and thirty women undergoing elective abortion (control group) were recruited during 2016 from gynecology outpatient clinics. We measured 25(OH) D, interleukin (IL)-17, IL-23, transforming growth factor β (TGF-β), VDR and 1-α-hydroxylase (CYP27B1) in decidual tissues collected during the abortion procedure. In the RSA group, 25(OH) D and TGF-β were significantly decreased while IL-17 and IL-23 were significantly increased compared with the control group. VDR expression was significantly decreased in the RSA group compared with the control group. Logistic regression analysis showed a significant negative correlation between 25(OH) D in decidual tissues and RSA. These results indicated that vitamin D concentrations in the decidua are associated with inflammatory cytokine production, suggesting that vitamin D and VDR may play a role in the etiology of RSA.


Subject(s)
Humans , Female , Pregnancy , Adult , Young Adult , Vitamin D/analogs & derivatives , Abortion, Habitual/metabolism , Receptors, Calcitriol/analysis , Decidua/chemistry , 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/analysis , Pregnancy Trimester, Third , Vitamin D/analysis , Vitamin D/metabolism , Vitamin D Deficiency/complications , Logistic Models , Risk Factors , Abortion, Habitual/etiology , Transforming Growth Factor beta/analysis , Receptors, Calcitriol/metabolism , Statistics, Nonparametric , Interleukin-17/analysis , Interleukin-23/analysis , 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/metabolism
18.
Article in Korean | WPRIM | ID: wpr-33718

ABSTRACT

BACKGROUND: Psoriasis is a chronic inflammatory skin disorder affecting approximately 1~3% of the general population. Ustekinumab is a recently developed human monoclonal antibody for psoriasis that binds to the p40 subunit shared by the interleukins IL-12 and IL-23. OBJECTIVE: The purpose of this study was to evaluate the effect of combination treatment with ustekinumab and topical agents in 30 Korean patients with psoriasis regarding different clinical parameters. METHODS: We retrospectively searched to identify patients with moderate-to-severe plaque-type psoriasis who had initiated treatment with ustekinumab between January 2012 and January 2016. Among them, our study was conducted in 30 patients with psoriasis who were treated with ustekinumab and topical agents for at least 16 weeks by analyzing their clinical charts and photographs. RESULTS: Overall, 16.7%, 93.3%, and 96.2% patients achieved PASI 75 response rates at weeks 4, 16, and 40, respectively. Furthermore, fifteen patients achieved 90% improvement in their PASI score at 100 weeks and five patients maintained their PASI score at 160 weeks. The efficacy of treatment with ustekinumab was different in sub-group analysis. Non-smokers enjoyed a higher therapeutic effect than did smokers. In addition, the therapeutic effect of ustekinumab was lower in the groups with psoriatic arthritis and nail psoriasis. However, it was not statistically significant. None of the patients experienced serious adverse events requiring the interruption of treatment. CONCLUSION: Combination treatment with ustekinumab and topical agents provides effective treatment results for Korean patients with psoriasis.


Subject(s)
Arthritis, Psoriatic , Follow-Up Studies , Humans , Interleukin-12 , Interleukin-23 , Interleukins , Psoriasis , Retrospective Studies , Skin , Ustekinumab
19.
Article in English | WPRIM | ID: wpr-16099

ABSTRACT

IL-12 and IL-23 are closely related in structure, and have been shown to play crucial roles in regulation of immune responses. However, little is known about the regulation of these cytokines in T cells. Here, we investigated the roles of PI3K and MAPK pathways in IL-12 and IL-23 production in human Jurkat T cells in response to Toxoplasma gondii and LPS. IL-12 and IL-23 production was significantly increased in T cells after stimulation with T. gondii or LPS. T. gondii and LPS increased the phosphorylation of AKT, ERK1/2, p38 MAPK, and JNK1/2 in T cells from 10 min post-stimulation, and peaked at 30–60 min. Inhibition of the PI3K pathway reduced IL-12 and IL-23 production in T. gondii-infected cells, but increased in LPS-stimulated cells. IL-12 and IL-23 production was significantly reduced by ERK1/2 and p38 MAPK inhibitors in T. gondii- and LPS-stimulated cells, but not in cells treated with a JNK1/2 inhibitor. Collectively, IL-12 and IL-23 production was positively regulated by PI3K and JNK1/2 in T. gondii-infected Jurkat cells, but negatively regulated in LPS-stimulated cells. And ERK1/2 and p38 MAPK positively regulated IL-12 and IL-23 production in Jurkat T cells. These data indicate that T. gondii and LPS induced IL-12 and IL-23 production in Jurkat T cells through the regulation of the PI3K and MAPK pathways; however, the mechanism underlying the stimulation of IL-12 and IL-23 production by T. gondii in Jurkat T cells is different from that of LPS.


Subject(s)
Cytokines , Humans , Interleukin-12 , Interleukin-23 , Jurkat Cells , p38 Mitogen-Activated Protein Kinases , Phosphorylation , T-Lymphocytes , Toxoplasma
20.
Article in English | WPRIM | ID: wpr-226342

ABSTRACT

OBJECTIVE: In vitro fertilization (IVF) is a well-known method for the treatment of infertility. The present study aimed to compare the differences between infertile women with successful and unsuccessful IVF outcomes regarding the expression of T helper (Th) cell transcription factors and a group of related cytokines before and after exposure to their husbands' seminal plasma. METHODS: This study was performed on 19 couples with unexplained infertility undergoing IVF treatment. Among the studied group, nine and 10 couples had successful and unsuccessful IVF outcomes, respectively. This study was carried out using real-time polymerase chain reaction. RESULTS: Before seminal plasma exposure, the expression levels of T-bet (p < 0.007), interferon-γ (p=0.013), and tumor necrosis factor (TNF)-α (p=0.017) were higher in the infertile women with IVF failure than in those with successful IVF outcomes, while those of GATA3 (p < 0.001), Foxp3 (p=0.001), and interleukin (IL)-35 (p < 0.003) were lower. After seminal exposure, the expression of T-bet (p=0.02), Rorc (p < 0.001), TNF-α (p=0.001), Foxp3 (p=0.02), and interferon-γ (p=0.001) increased in the unsuccessful IVF group, while the expression of Foxp3 (p=0.02), Rorc (p < 0.001), IL-23 (p=0.04), IL-17 (p=0.02), IL-6 (p < 0.001), transforming growth factor-β (p=0.01), and IL-35 (p < 0.001) increased in the successful IVF group. CONCLUSION: In summary, IVF failure was associated with imbalanced Th1/Th2/Th17/Treg responses. Moreover, our results show that seminal plasma might have a positive effect on IVF outcomes via changes in peripheral blood T cell subsets.


Subject(s)
Cytokines , Family Characteristics , Female , Fertilization in Vitro , Humans , In Vitro Techniques , Infertility , Interleukin-17 , Interleukin-23 , Interleukin-6 , Interleukins , Methods , Real-Time Polymerase Chain Reaction , Semen , T-Lymphocyte Subsets , T-Lymphocytes, Helper-Inducer , Transcription Factors , Tumor Necrosis Factor-alpha
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