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2.
Artículo en Inglés | MEDLINE | ID: mdl-38716221

RESUMEN

Background: Crohn's disease (CD) is a chronic inflammatory bowel disease with significant morbidity, affecting millions worldwide. The intricacies of immune responses in CD, especially post-treatment, remain a vital area of exploration. While memory T (Tm)-cell subsets play a pivotal role in adaptive immunity, their specific function in patients with CD after treatment is not well-understood. This study aims to investigate the effect and function of Tm-cell subsets in these patients, addressing a crucial knowledge gap in the context of CD therapeutics. Methods: A total of eight patients diagnosed with CD were selected based on predefined inclusion criteria. All patients were treated with either anti-inflammatory agents, immunosuppressive drugs, or a combination of both. For comparison, healthy donors were enrolled based on exclusion of autoimmune or inflammatory diseases. Peripheral blood mononuclear cells (PBMCs) and lymphocytes were isolated from blood and lymph node tissue respectively. The phenotype and cytokine production of T lymphocytes from both CD patients and healthy donors were analyzed using flow cytometry. Statistical comparisons of the outcomes between CD patients and healthy donors were made using Mann-Whitney test (two-tailed) and Student t-test. Results: Post-treatment CD patients exhibited an altered T cell distribution with a notable increase in CD8+ T cells in PBMCs (P=0.0005), and altered frequencies of CD4+ and CD8+ T cells in mesenteric lymph nodes (MLNs). Tm cells showed decreased interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) production, with significant alterations in the frequency of IFN-γ-producing CD8+ stem cell-like Tm (Tscm) cells in lesions of the MLNs from patients with CD (CD-M-Lys) compared to healthy MLNs from patients with CD (N-M-Lys) (P=0.0152). Differences in tissue-resident Tm (Trm)-cell subset frequencies were observed between the MLNs and small intestinal mucosa in CD patients. Conclusions: The treatments with anti-inflammatory agents and/or immunosuppressive drugs have a significant effect on the frequency and function of Tm-cell subsets. Clinically, these findings suggest a potential therapeutic avenue in modulating Tm-cell responses, which might be particularly beneficial for conditions where immune response modulation is crucial. Further clinical studies are warranted to explore the full therapeutic implications of these findings.

3.
Mol Immunol ; 171: 66-76, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38795686

RESUMEN

Chronic inflammation has long been considered the characteristic feature of type II diabetes mellitus (T2DM) Immunopathogenesis. Pro-inflammatory cytokines are considered the central drivers of the inflammatory cascade leading to ß-cell dysfunction and insulin resistance (IR), two major pathologic events contributing to T2DM. Analyzing the cytokine profile of T2DM patients has also introduced interleukin-17 (IL-17) as an upstream regulator of inflammation, regarding its role in inducing the nuclear factor-kappa B (NF-κB) pathway. In diabetic tissues, IL-17 induces the expression of inflammatory cytokines and chemokines. Hence, IL-17 can deteriorate insulin signaling and ß-cell function by activating the JNK pathway and inducing infiltration of neutrophils into pancreatic islets, respectively. Additionally, higher levels of IL-17 expression in patients with diabetic complications compared to non-complicated individuals have also proposed a role for IL-17 in T2DM complications. Here, we highlight the role of IL-17 in the Immunopathogenesis of T2DM and corresponding pathways, recent advances in preclinical and clinical studies targeting IL-17 in T2DM, and corresponding challenges and possible solutions.


Asunto(s)
Diabetes Mellitus Tipo 2 , Interleucina-17 , Humanos , Diabetes Mellitus Tipo 2/inmunología , Interleucina-17/inmunología , Animales , Inflamación/inmunología , Células Secretoras de Insulina/inmunología , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patología , Complicaciones de la Diabetes/inmunología , Resistencia a la Insulina/inmunología , Transducción de Señal/inmunología
4.
Hematol Rep ; 15(4): 684-695, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38132277

RESUMEN

BACKGROUND: Platelet "Microvesicles" (MVs) are studied for their role in blood coagulation and inflammation. The study aimed to establish if MVs are related to age, plasma levels of inflammation, coagulation, and fibrinolysis markers in healthy individuals. METHODS: We prospectively enrolled volunteers aged over 18 years. MVs, plasma levels of C-reactive protein (CRP), Interleukin 6 (IL-6), Interleukin 10 (IL-10), Interleukin 17 (IL-17), and transforming growth factor ß (TGF-ß), fibrinogen, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (VWF), homocysteine, factor VII (FVII), thrombin activatable fibrinolysis inhibitor (TAFI), and Protein S were tested. RESULTS: A total of 246 individuals (median age 65 years ("IQR"54-72)) were evaluated. Both univariate analysis and logistic regression models showed that MVs positively correlate with age, CRP, IL-6, IL-10, IL-17, TGF-ß, fibrinogen, PAI-1, VWF, FVII, and homocysteine, while inversely correlating with TAFI and Protein S. The ROC curve analysis performed to identify a cut off for MV values (700 kMP) showed a good accuracy with over-range cytokines fibrinolysis factor and coagulation markers. CONCLUSIONS: To the best of our knowledge, this study is the first to correlate MVs with an entire panel of cardiovascular risk factors in healthy individuals. A future possible role of MVs in screening exams is suggested.

5.
Oncoimmunology ; 12(1): 2261326, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37808403

RESUMEN

IL-17 immune responses in cancer are controversial, with both tumor-promoting and tumor-repressing effects observed. To clarify the role of IL-17 signaling in cancer progression, we used syngeneic tumor models from different tissue origins. We found that deficiencies in host IL-17RA or IL-17A/F expression had varying effects on the in vivo growth of different solid tumors including melanoma, sarcoma, lymphoma, and leukemia. In each tumor type, the absence of IL-17 led to changes in the expression of mediators associated with inflammation and metastasis in the tumor microenvironment. Furthermore, IL-17 signaling deficiencies in the hosts resulted in decreased anti-tumor CD8+ T cell immunity and caused tumor-specific changes in several lymphoid cell populations. Our findings were associated with distinct patterns of IL-17A/F cytokine and receptor subunit expression in the injected tumor cell lines. These patterns affected tumor cell responsiveness to IL-17 and downstream intracellular signaling, leading to divergent effects on cancer progression. Additionally, we identified IL-17RC as a critical determinant of the IL-17-mediated response in tumor cells and a potential biomarker for IL-17 signaling effects in tumor progression. Our study offers insight into the molecular mechanisms underlying IL-17 activities in cancer and lays the groundwork for developing personalized immunotherapies.


Asunto(s)
Neoplasias , Receptores de Interleucina-17 , Humanos , Receptores de Interleucina-17/genética , Receptores de Interleucina-17/metabolismo , Interleucina-17 , Transducción de Señal , Linfocitos T CD8-positivos , Inflamación , Neoplasias/genética
6.
Prostate ; 83(15): 1430-1445, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37517867

RESUMEN

BACKGROUND: Melittin is a small molecule polypeptide extracted from the abdominal cavity of bees, which is used to treat inflammatory diseases and relieve pain. However, the antitumor effect of melittin and its mechanisms remain unclear, especially in castration-resistant prostate cancer (CRPC). METHODS: Through CCK-8 assay, colony formation assay, wound healing assay and Transwell migration assay, we explored the effect of melittin on CRPC cell lines. In addition, with microarray analysis, gene ontology analysis and kyoto encyclopedia of genes and genomes analysis, this study identified key genes and signaling pathways that influence the growth of PC-3 cells. Meanwhile, the effect of melittin on CRPC was also verified through subcutaneous tumor formation experiments. Finally, we also tested the relevant indicators of human prostate cancer (PCa) specimens through immunohistochemistry and H&E stating. RESULTS: Here, melittin was verified to inhibit the cell proliferation and migration of CPRC. Moreover, RNA-sequence analysis demonstrated that Interleukin-17 (IL-17) signaling pathway gene Lipocalin-2 (LCN2) was downregulated by melittin treatment in CRPC. Further investigation revealed that overexpression of LCN2 was able to rescue tumor suppression and cisplatin sensitivity which melittin mediated. Interestingly, the expression of LCN2 is highly related to metastasis in PCa. CONCLUSIONS: In brief, our study indicates that LCN2 plays an oncogenic role in CRPC and melittin may be selected as an attractive candidate for CRPC therapy.


Asunto(s)
Cisplatino , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Animales , Lipocalina 2/genética , Lipocalina 2/metabolismo , Lipocalina 2/farmacología , Cisplatino/farmacología , Cisplatino/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Interleucina-17/metabolismo , Interleucina-17/farmacología , Meliteno/farmacología , Meliteno/metabolismo , Línea Celular Tumoral , Transducción de Señal , Proliferación Celular , Movimiento Celular
7.
Int J Mol Sci ; 24(12)2023 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-37373022

RESUMEN

Elucidating the inflammatory mechanisms underlying formation and progression of oral squamous cell carcinoma (OSCC) is crucial for discovering new targeted therapeutics. The proinflammatory cytokine IL-17 has proven roles in tumor formation, growth, and metastasis. The presence of IL-17 is demonstrated in both in vitro and in vivo models, and in OSCC patients, is mostly accompanied by enhanced proliferation and invasiveness of cancer cells. Here we review the known facts regarding the role of IL-17 in OSCC pathogenesis, namely the IL-17 mediated production of proinflammatory mediators that mobilize and activate myeloid cells with suppressive and proangiogenic activities and proliferative signals that directly induce proliferation of cancer cells and stem cells. The possibility of a potential IL-17 blockade in OSCC therapy is also discussed.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Neoplasias de la Boca/etiología , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas/etiología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas de Cabeza y Cuello , Interleucina-17 , Proliferación Celular , Línea Celular Tumoral
8.
Int J Mol Sci ; 24(12)2023 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-37373070

RESUMEN

Oil-Gan, also known as emblica, is the fruit of the genus Phyllanthus emblica L. The fruits are high in nutrients and display excellent health care functions and development values. The primary aim of this study was to investigate the activities of ethyl acetate extract from Phyllanthus emblica L. (EPE) on type 1 diabetes mellitus (T1D) and immunoregulatory activities in non-obese diabetes (NOD) mice with spontaneous and cyclophosphamide (Cyp)-accelerated diabetes. EPE was vehicle-administered to spontaneous NOD (S-NOD) mice or Cyp-accelerated NOD (Cyp-NOD) mice once daily at a dose of 400 mg/kg body weight for 15 or 4 weeks, respectively. At the end, blood samples were collected for biological analyses, organ tissues were dissected for analyses of histology and immunofluorescence (IF) staining (including expressions of Bcl and Bax), the expression levels of targeted genes by Western blotting and forkhead box P3 (Foxp3), and helper T lymphocyte 1 (Th1)/Th2/Th17/Treg regulatory T cell (Treg) cell distribution by flow cytometry. Our results showed that EPE-treated NOD mice or Cyp-accelerated NOD mice display a decrease in levels of blood glucose and HbA1c, but an increase in blood insulin levels. EPE treatment decreased blood levels of IFN-γ and tumor necrosis α (TNF-α) by Th1 cells, and reduced interleukin (IL)-1ß and IL-6 by Th17 cells, but increased IL-4, IL-10, and transforming growth factor-ß1 (TGF-ß1) by Th2 cells in both of the two mice models by enzyme-linked immunosorbent assay (ELISA) analysis. Flow cytometric data showed that EPE-treated Cyp-NOD mice had decreased the CD4+ subsets T cell distribution of CD4+IL-17 and CD4+ interferon gamma (IFN-γ), but increased the CD4+ subsets T cell distribution of CD4+IL-4 and CD4+Foxp3. Furthermore, EPE-treated Cyp-NOD mice had decreased the percentage per 10,000 cells of CD4+IL-17 and CD4+IFNγ, and increased CD4+IL-4 and CD4+Foxp3 compared with the Cyp-NOD Con group (p < 0.001, p < 0.05, p < 0.05, and p < 0.05, respectively). For target gene expression levels in the pancreas, EPE-treated mice had reduced expression levels of inflammatory cytokines, including IFN-γ and TNF-α by Th1 cells, but increased expression levels of IL-4, IL-10, and TGF-1ß by Th2 cells in both two mice models. Histological examination of the pancreas revealed that EPE-treated mice had not only increased pancreatic insulin-expressing ß cells (brown), and but also enhanced the percentage of Bcl-2 (green)/Bax (red) by IF staining analyses of islets compared with the S-NOD Con and the Cyp-NOD Con mice, implying that EPE displayed the protective effects of pancreas ß cells. EPE-treated mice showed an increase in the average immunoreactive system (IRS) score on insulin within the pancreas, and an enhancement in the numbers of the pancreatic islets. EPE displayed an improvement in the pancreas IRS scores and a decrease in proinflammatory cytokines. Moreover, EPE exerted blood-glucose-lowering effects by regulating IL-17 expressions. Collectively, these results implied that EPE inhibits the development of autoimmune diabetes by regulating cytokine expression. Our results demonstrated that EPE has a therapeutic potential in the preventive effects of T1D and immunoregulation as a supplementary.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Phyllanthus emblica , Ratones , Animales , Diabetes Mellitus Tipo 1/genética , Interleucina-10/metabolismo , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Ratones Endogámicos NOD , Interleucina-17 , Phyllanthus emblica/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/uso terapéutico , Interleucina-4/metabolismo , Proteína X Asociada a bcl-2 , Citocinas/uso terapéutico , Interferón gamma/metabolismo , Insulina/uso terapéutico , Linfocitos T Reguladores , Ciclofosfamida/efectos adversos , Factores de Transcripción Forkhead
9.
Adv Rheumatol ; 63(1): 15, 2023 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-36973825

RESUMEN

BACKGROUND: Secukinumab has shown high efficacy in randomized controlled trials in both ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Here, we investigated its real-life effectiveness and tolerability in a cohort of AS and PsA patients. METHODS: We retrospectively analyzed medical records of outpatients with AS or PsA treated with secukinumab between December 2017 and December 2019. ASDAS-CRP and DAS28-CRP scores were used to measure axial and peripheral disease activity in AS and PsA, respectively. Data were collected at baseline and after 8, 24, and 52 weeks of treatment. RESULTS: Eighty-five adult patients with active disease (29 with AS and 56 with PsA; 23 males and 62 females) were treated. Overall, mean disease duration was 6.7 years and biologic-naïve patients were 85%. Significant reductions in ASDAS-CRP and DAS28-CRP were observed at all time-points. Body weight (in AS) and disease activity status at baseline (particularly in PsA) significantly affected disease activity changes. ASDAS-defined inactive disease and DAS28-defined remission were achieved in comparable proportions between AS and PsA patients, at both 24 weeks (45% and 46%) and 52 weeks (65.5% and 68%, respectively); male sex was found an independent predictor of positive response (OR 5.16, P = 0.027). After 52 weeks, achievement of at least low disease activity and drug retention were observed in 75% of patients. Secukinumab was well-tolerated and only mild injection-site reactions were recorded in 4 patients. CONCLUSION: In a real-world setting, secukinumab confirmed great effectiveness and safety in both AS and PsA patients. The influence of gender on treatment response deserves further attention.


Asunto(s)
Artritis Psoriásica , Espondilitis Anquilosante , Adulto , Femenino , Humanos , Masculino , Espondilitis Anquilosante/tratamiento farmacológico , Artritis Psoriásica/tratamiento farmacológico , Estudios Retrospectivos , Italia
11.
Adv Rheumatol ; 63: 15, 2023. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1447142

RESUMEN

Abstract Background Secukinumab has shown high efficacy in randomized controlled trials in both ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Here, we investigated its real-life effectiveness and tolerability in a cohort of AS and PsA patients. Methods We retrospectively analyzed medical records of outpatients with AS or PsA treated with secukinumab between December 2017 and December 2019. ASDAS-CRP and DAS28-CRP scores were used to measure axial and peripheral disease activity in AS and PsA, respectively. Data were collected at baseline and after 8, 24, and 52 weeks of treatment. Results Eighty-five adult patients with active disease (29 with AS and 56 with PsA; 23 males and 62 females) were treated. Overall, mean disease duration was 6.7 years and biologic-naïve patients were 85%. Significant reductions in ASDAS-CRP and DAS28-CRP were observed at all time-points. Body weight (in AS) and disease activity status at baseline (particularly in PsA) significantly affected disease activity changes. ASDAS-defined inactive disease and DAS28-defined remission were achieved in comparable proportions between AS and PsA patients, at both 24 weeks (45% and 46%) and 52 weeks (65.5% and 68%, respectively); male sex was found an independent predictor of positive response (OR 5.16, P = 0.027). After 52 weeks, achievement of at least low disease activity and drug retention were observed in 75% of patients. Secukinumab was well-tolerated and only mild injection-site reactions were recorded in 4 patients. Conclusion In a real-world setting, secukinumab confirmed great effectiveness and safety in both AS and PsA patients. The influence of gender on treatment response deserves further attention.

12.
Zhongguo Zhen Jiu ; 42(8): 853-6, 2022 Aug 12.
Artículo en Chino | MEDLINE | ID: mdl-35938326

RESUMEN

OBJECTIVE: To compare the clinical therapeutic effect on acute ischemic stroke between Naochang Tongtiao acupuncture (acupuncture for brain-gut homology) and conventional acupuncture, and to explore the possible mechanism. METHODS: A total of 64 patients with acute ischemic stroke were randomized into an observation group and a control group, 32 cases in each one. Basic western medical therapy was adopted in both groups. In the observation group, Naochang Tongtiao acupuncture was applied at anterior oblique line of vertex-temporal, Zhongwan (CV 12), Guanyuan (CV 4), Tianshu (ST 25), Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39). In the control group, conventional acupuncture was applied. The treatment was given once a day, 6 days a week for 3 weeks in both groups. Before and after treatment, National Institution of Health stroke scale (NIHSS) score, serum levels of interleukin-17 (IL-17) and hypersensitive C reactive protein (hs-CRP), and plasma level of trimethylamine oxide (TMAO) were compared in the two groups. RESULTS: After treatment, NIHSS scores, serum levels of IL-17 and hs-CRP, and plasma levels of TMAO were decreased compared before treatment in both groups (P<0.01), and those in the observation group were lower than the control group (P<0.05). CONCLUSION: Naochang Tongtiao acupuncture can improve the nerve function in patients with acute ischemic stroke, its therapeutic effect is superior to conventional acupuncture, the mechanism may relate to the regulation on inflammatory reaction and the level of intestinal flora metabolite.


Asunto(s)
Terapia por Acupuntura , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Puntos de Acupuntura , Eje Cerebro-Intestino , Proteína C-Reactiva , Humanos , Interleucina-17 , Accidente Cerebrovascular Isquémico/terapia , Metilaminas , Accidente Cerebrovascular/terapia , Resultado del Tratamiento
13.
New Microbiol ; 45(3): 213-218, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35920877

RESUMEN

Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS- CoV-2-specific IgG than patients with mild symptoms. In this retrospective study we considered different categories of patients defined as "vulnerable" because affected by other pathologies, such as patients with genetic and cardiovascular diseases; patients with autoimmune dermatological dis- ease; kidney and lung transplant patients, and pregnant women because the prevalence of Covid-19 infection during pregnancy is not known. This study was performed at IRCCS San Matteo Hospital in Pavia, North Italy, a zone considered at high risk during the COVID-19 pandemic from June to December 2020. None of the positive screened patients had symptoms of COVID-19 infection at the time of inclusion in this study.


Asunto(s)
COVID-19 , Pandemias , Anticuerpos Antivirales , Femenino , Humanos , Inmunoglobulina G , Embarazo , Estudios Retrospectivos , SARS-CoV-2
14.
Front Immunol ; 13: 848168, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35860254

RESUMEN

In juvenile idiopathic arthritis (JIA) inflammatory T cells and their produced cytokines are drug targets and play a role in disease pathogenesis. Despite their clinical importance, the sources and types of inflammatory T cells involved remain unclear. T cells respond to polarizing factors to initiate types of immunity to fight infections, which include immunity types 1 (T1), 2 (T2), and 3 (T17). Polarizing factors drive CD4+ T cells towards T helper (Th) cell subtypes and CD8+ T cells towards cytotoxic T cell (Tc) subtypes. T1 and T17 polarization are associated with autoimmunity and production of the cytokines IFNγ and IL-17 respectively. We show that JIA and child healthy control (HC) peripheral blood mononuclear cells are remarkably similar, with the same frequencies of CD4+ and CD8+ naïve and memory T cell subsets, T cell proliferation, and CD4+ and CD8+ T cell subsets upon T1, T2, and T17 polarization. Yet, under T1 polarizing conditions JIA cells produced increased IFNγ and inappropriately produced IL-17. Under T17 polarizing conditions JIA T cells produced increased IL-17. Gene expression of IFNγ, IL-17, Tbet, and RORγT by quantitative PCR and RNA sequencing revealed activation of immune responses and inappropriate activation of IL-17 signaling pathways in JIA polarized T1 cells. The polarized JIA T1 cells were comprised of Th and Tc cells, with Th cells producing IFNγ (Th1), IL-17 (Th17), and both IFNγ-IL-17 (Th1.17) and Tc cells producing IFNγ (Tc1). The JIA polarized CD4+ T1 cells expressed both Tbet and RORγT, with higher expression of the transcription factors associated with higher frequency of IL-17 producing cells. T1 polarized naïve CD4+ cells from JIA also produced more IFNγ and more IL-17 than HC. We show that in JIA T1 polarization inappropriately generates Th1, Th17, and Th1.17 cells. Our data provides a tool for studying the development of heterogeneous inflammatory T cells in JIA under T1 polarizing conditions and for identifying pathogenic immune cells that are important as drug targets and diagnostic markers.


Asunto(s)
Artritis Juvenil , Interleucina-17 , Linfocitos T CD8-positivos/metabolismo , Niño , Citocinas , Humanos , Interleucina-17/metabolismo , Leucocitos Mononucleares , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Células TH1
15.
Front Cardiovasc Med ; 9: 896810, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35651907

RESUMEN

Introduction: Various cytokines were involved in the process of atherosclerosis, and their serum levels were correlated with coronary artery disease (CAD) to varying degrees. However, there were limited reports about the correlation between serum cytokines and the severity of coronary atherosclerotic lesion in patients with non-acute myocardial infarction (AMI). The purpose of this study was to investigate the relationship between serum cytokines and the severity of CAD, and identify the predictors of severe CAD in patients suspected to have CAD but AMI had been ruled out. Methods: A total of 502 patients who had suspected CAD and underwent coronary angiography were enrolled. The serum levels of IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, TNF-α, IFN-α,and IFN-γ were determined by multiplexed particle-based flow cytometric assays technology. And the severity of CAD was evaluated by Gensini score (GS). Results: The serum levels of IL-4, IL-12p70, IL-17, and IFN-α were significantly lower in the severe CAD group (GS≥30) than those in the non-severe CAD group (GS < 30). And IL-12p70 and IL-17 were negatively correlated with the severity of CAD. Multivariate logistic regression analyses demonstrated that two serum cytokines (IL-12p70 and IL-17), one clinical protective factor (HDL-C), and two clinical risk factors (gender and diabetes) were the independent predictors of severe CAD. ROC curve analysis showed that multivariate mode combined these predictors had a good performance in predicting severe CAD. Conclusion: The combination of serum cytokines (IL-12p70 and IL-17) and clinical risk factors (HDL-C, gender, and diabetes) may help identify patients with more severe coronary artery lesions from those with suspected CAD but not AMI, and may contribute to guiding the risk stratification for patients with chest discomfort in health care facilities without sufficient medical resources (especially cardiac catheterization resources).

16.
Drugs Today (Barc) ; 58(6): 273-282, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35670705

RESUMEN

Psoriasis is a chronic, immune-mediated, inflammatory skin disease, affecting 1% to 3% of the population in Western countries. Due to advances in the understanding of psoriasis pathogenesis, in particular, the role of the interleukin-23 (IL-23)/T-helper 17 (Th17) immune axis, highly effective, targeted biologic therapies have been developed, shifting the psoriasis treatment paradigm. However, some patients do not respond or lose response to these novel therapies. Bimekizumab is a first-in-class humanized monoclonal immunoglobulin G1 (IgG1) antibody that potently and selectively inhibits both IL-17A and IL-17F, functioning as a dual inhibitor. All bimekizumab studies have shown high efficacy in psoriasis patients. Its onset of response was rapid and sustained for periods up to 60 weeks. In active-comparator trials to date, bimekizumab was superior to adalimumab (BE SURE), ustekinumab (BE VIVID) and secukinumab (BE RADIANT). It has demonstrated a consistent safety profile and high tolerability. The most common adverse events were largely restricted to mucosal candidiasis. Dual inhibition of IL-17A and IL-17F with bimekizumab showed to be a highly effective treatment for psoriasis, and the product is already approved for treatment of moderate to severe plaque psoriasis in Europe, Canada and Japan.


Asunto(s)
Interleucina-17 , Psoriasis , Anticuerpos Monoclonales , Anticuerpos Monoclonales Humanizados , Enfermedad Crónica , Humanos , Psoriasis/tratamiento farmacológico , Resultado del Tratamiento
17.
Mil Med Res ; 9(1): 21, 2022 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-35550651

RESUMEN

Idiopathic pulmonary fibrosis (IPF) is a fatal chronic interstitial lung disease with no established treatment and is characterized by progressive scarring of the lung tissue and an irreversible decline in lung function. Chronic inflammation has been demonstrated to be the pathological basis of fibrosis. Emerging studies have revealed that most interleukin-17 (IL-17) isoforms are essential for the mediation of acute and chronic inflammation via innate and adaptive immunity. Overexpression or aberrant expression of IL-17 cytokines contributes to various pathological outcomes, including the initiation and exacerbation of IPF. Here, we aim to provide an overview of IL-17 family members in the pathogenesis of IPF.


Asunto(s)
Fibrosis Pulmonar Idiopática , Citocinas , Fibrosis , Humanos , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/patología , Inflamación , Interleucina-17
18.
Artículo en Inglés | MEDLINE | ID: mdl-36613090

RESUMEN

The aim of the study was to assess the role of concentrations of interleukin-17 (IL-17), placental growth factor (PlGF) and soluble endoglin (sENG), as well as the PlGF/sENG ratio in pregnancy complicated by pre-eclampsia (PE) and normal pregnancy. The concentrations of IL-17, PlGF and sENG were measured with the use of immunoenzymatic methods. The concentrations of IL-17 were significantly higher in PE patients when compared to control patients. In the group of patients with PE, the levels of IL-17 positively correlated with systolic blood pressure. On the other hand, IL-17 negatively correlated with neonatal birth weight. The concentrations of PLGF were significantly lower and sENG significantly higher in studied patients when compared to controls. The PlGF/sENG ratio in the PE group was significantly lower when compared to healthy third trimester pregnant patients. In the study group, negative correlations were observed between the sENG concentrations and thrombocyte levels. The higher concentrations of IL-17 in PE could suggest its role as an inflammatory agent in the pathogenesis of the syndrome. Moreover, the negative correlation between IL-17 and a neonatal birth weight could suggest the role of the cytokine in the development of fetal growth restriction (FGR) associated with PE. It seems possible that IL-17 can be a useful marker of the risk of FGR in pregnancy complicated by PE. Furthermore, the results suggested the potential role of sENG and the PlGF/sENG ratio in the prediction of adverse outcomes such as HELLP syndrome and DIC.


Asunto(s)
Preeclampsia , Proteínas Gestacionales , Embarazo , Recién Nacido , Humanos , Femenino , Endoglina , Factor de Crecimiento Placentario , Preeclampsia/epidemiología , Resultado del Embarazo/epidemiología , Interleucina-17 , Receptores de Superficie Celular , Peso al Nacer , Biomarcadores , Antígenos CD , Receptor 1 de Factores de Crecimiento Endotelial Vascular
19.
Clin Biochem ; 98: 29-34, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34496287

RESUMEN

BACKGROUND AND PURPOSE: Inflammation plays a crucial role in brain damage following stroke. Here, we evaluate interleukin 23 (IL-23) and interleukin 17 (IL-17) in the inflammatory process and its relations with neurological findings of patients with acute ischemic stroke (AIS). MATERIAL AND METHODS: Fifty consecutive patients with AIS admitted to our hospital within 24 h of stroke onset were enrolled in a prospective cohort study. Serum IL-23 and IL-17 were measured in the first, third and fifth day after the stroke. Neurological stroke severity were determined with the National Institutes of Health Stroke Scale (NIHSS) and with the modified Rankin Scale (mRS) within 24 h of the acute event, on the third and fifth day after the stroke, and at the time of hospital discharge. RESULTS: Both neurological scores for stroke outcome at hospital discharge were related to IL-23 protein within 24 h and on the fifth day, but with low stroke outcome predictive values. The other measurements did not show predictive capacity for stroke outcome. There was a significant increase in median serum concentrations of IL-23 on the fifth day (p < 0.001) and in IL-17 median levels on the third day compared to the first 24 h after the acute injury (p < 0.001). However, there was no correlation between IL-23 and IL-17 levels with neurological outcomes at hospital discharge or after four years. CONCLUSION: IL-23 and IL-17 increase after stroke, but had no sufficient discriminative capacity to be of clinical use as outcome stroke predictors.


Asunto(s)
Interleucina-17/sangre , Interleucina-23/sangre , Accidente Cerebrovascular Isquémico/sangre , Adulto , Biomarcadores/sangre , Femenino , Humanos , Accidente Cerebrovascular Isquémico/diagnóstico , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Tiempo
20.
Int Immunopharmacol ; 100: 108160, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34583123

RESUMEN

BACKGROUND: Psoriasis is a chronic skin condition associated with interleukin-23/interleukin-17 (IL-23/IL-17) pathway. Recent evidence declares that angiotensin II (Ang II) induces a potent IL-17-related inflammation. Meanwhile, Losartan, an angiotensin one receptor (AT1R) antagonist, attenuates the TH17-related responses. Therefore, we investigated the possible beneficial effects of topically applied Losartan1% ointment on imiquimod (IMQ)-induced psoriasis in mice. METHOD: Psoriasis was induced in mice consecutively for five days by topical IMQ on the shaved back. The IMQ-induced psoriasis was treated via topical administration of Losartan1% twice a day. The severity of skin inflammation was evaluated employing Psoriasis Area and Severity Index (PASI) scores. Subsequently, the skin samples were assessed using Baker's scoring system, stereological studies, and biochemical assessment with real-time PCR and immunohistochemistry. RESULTS: IMQ administration induced plaque-type psoriasis and skin inflammation. We characterized psoriatic lesions by hyperkeratosis, Munro abscess, rete ridges, and marked T-cell infiltrates. IMQ significantly increased epidermal volume, mRNA expression of IL-17a, IL-23, Ang II, AT1R, and TNF-α levels compared with the Placebo group. Topical administration of Losartan1% on IMQ-induced psoriasis significantly reduced the PASI scores and alleviated the erythema and scaling. The treatment significantly decreased the psoriatic thickness and dermal T-cell infiltration. Regarding biochemical assessment, Losartan1% considerably reduced the IMQ-induced increase of IL-17a, Ang II, and AT1R expression in the skin. CONCLUSION: Topical Losartan1% significantly alleviates psoriasis by reducing AT1R and IL-17a expression. Our results introduce AT1Rs as a promising therapeutic target in psoriasis and represent a link between angiotensin and TH17-related inflammation. However, the effects of AngII-AT1R systems on IL-17 signaling need to be confirmed by further investigations.


Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Antiinflamatorios/administración & dosificación , Losartán/administración & dosificación , Psoriasis/prevención & control , Piel/efectos de los fármacos , Administración Cutánea , Animales , Modelos Animales de Enfermedad , Imiquimod , Interleucina-17/metabolismo , Masculino , Ratones , Pomadas , Psoriasis/inducido químicamente , Psoriasis/metabolismo , Psoriasis/patología , Receptor de Angiotensina Tipo 1/metabolismo , Piel/metabolismo , Piel/patología , Células Th17/efectos de los fármacos , Células Th17/metabolismo
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