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1.
An Bras Dermatol ; 94(6): 677-683, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31789253

RESUMO

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.


Assuntos
Glossite Migratória Benigna/patologia , Psoríase/patologia , Células Th17/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos/análise , Biópsia , Estudos Transversais , Feminino , Glossite Migratória Benigna/imunologia , Humanos , Imuno-Histoquímica , Interleucina-17/imunologia , Interleucina-23/imunologia , Interleucina-6/imunologia , Queratinócitos/patologia , Masculino , Pessoa de Meia-Idade , Psoríase/imunologia , Índice de Gravidade de Doença , Células Th17/imunologia , Adulto Jovem
3.
J Environ Pathol Toxicol Oncol ; 38(3): 285-295, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679314

RESUMO

Psoriasis is an autoregulated immune and inflammation-based skin disease affecting approximately 3-4% of the worldwide population. Pinitol, conservatively used in ayurvedic medicine, has been shown to disclose an antiinflammatory effect, hold back the T-helper cells, and postpone cardiovascular diseases. In the present study we aimed to reveal the effect of D-pinitol on imiquimod (IMQ)-induced psoriasis-like skin inflammation in a mouse model via the nuclear factor-κB (NF-κB) pathway genes. In the current study, we found that D-pinitol ameliorated the skin abrasion and abridged epithelial thickness, inflammation numbers, and collagen-occupied regions in IMQ-induced psoriasis-like mice. The same results (epithelial thickness, inflammation numbers, and collagen-occupied regions) we achieved in dorsal skin regions. In addition, D-pinitol modified the lipid profile and antioxidant enzyme levels, which means that the IMQ-induced group showed elevated malondialdehyde when compared to D-pinitol. Downregulated expression of glutathione, superoxide dismutase, and catalase in the IMQ-induced group was incomparable with D-pinitol, control, and standard group. Additionally, inflammatory and NF-kB pathway gene levels in the psoriatic mouse skin, which includes tumor necrosis factor-α, interleukin [IL]-6, IL-17A, IL-23,TRAF3, NIK, IKKα, and RelB, were dramatically increased or decreased by treatment with D-pinitol. Histological and morphometric studies disclose the efficiency of D-pinitol. Finally, we found that D-pinitol reserved the TRAF3, NIK, IKKα, and RelB in the psoriatic skin, signifying that it restrains the commencement of NF-κB signaling pathways. The present results suggest that D-pinitol could prove to have tremendous preventive potential against the treatment and prevention of inflammatory disease.


Assuntos
Anti-Inflamatórios/farmacologia , Imiquimode/imunologia , Inflamação/tratamento farmacológico , Inositol/análogos & derivados , Psoríase/tratamento farmacológico , Animais , Inflamação/induzido quimicamente , Inflamação/imunologia , Inositol/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/imunologia , Psoríase/imunologia
4.
Expert Opin Drug Metab Toxicol ; 15(11): 913-925, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31623470

RESUMO

Introduction: The treatment of psoriasis with conventional topical therapies and disease-modifying anti-rheumatic drugs (DMARDs) is often linked to unsatisfactory outcomes and the risk of serious adverse events. Over the last decades, research advances in understanding the role of tumor necrosis factor alpha (TNF α) and other cytokines in the pathogenesis of psoriasis have driven the introduction of biologic agents targeting specific immune mediators in everyday clinical practice. TNF α inhibitors are a consolidated treatment option for patients with moderate-to-severe disease with remarkable efficacy and a reassuring safety profile.Areas covered: The PubMed database was searched using combinations of the following keywords: psoriasis, TNF α inhibitors, biologic therapy, pharmacodynamics, adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, adverse effects. The aim of this review is to describe the pharmacodynamic profile of anti-TNF α inhibitors, currently approved by the European Medicines Agency (EMA) for the treatment of psoriasis, focusing on related clinical implications, also in comparison to the new generation biological therapies targeting the interleukin 23/interleukin 17 axis.Expert opinion: Pharmacodynamics of TNF α inhibitors should be fully considered in planning patient's therapy strategies, especially in case of secondary failures, poor adherence to treatment, instable psoriasis, high risk of infection, pregnant or lactating women, metabolic comorbidities, coexistence of other immune-mediated inflammatory diseases.


Assuntos
Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Antirreumáticos/farmacologia , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/farmacologia , Desenvolvimento de Medicamentos , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/farmacologia , Adesão à Medicação , Psoríase/imunologia , Psoríase/patologia , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/metabolismo
5.
Expert Opin Drug Saf ; 18(11): 1031-1041, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31479282

RESUMO

Introduction: Psoriasis is a chronic inflammatory disease and affects about 10% of the world's population. Psoriasis is associated with a number of comorbidities. Biologic therapies for the treatment of moderate-severe plaque psoriasis include tumor necrosis factor α inhibitors (TNFi), and newer molecules targeting IL-12 and 23, blocking p40 subunit, or targeting subunit p19 of IL-23 and other molecules blocking IL-17A, or directed against the IL-17 receptor. Areas covered: Anti-interleukin drugs show great improvement in disease control and on the other hand are not affected by important adverse reactions of older compounds. Approach to chronic disease affected patients, in particular, and to patients with multiple comorbidities is revolutionized by novel molecules that are safer and more manageable. Expert opinion: A recent work suggests that pro-fibrogenic cytokines, IL-17, might be important player of liver damage and even in regulation of obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD) pathogenesis. Choosing to interfere with IL-23/Il-17 axis, definitely, is like acting against psoriatic march and in a parallel way against its comorbidities.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/imunologia , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Produtos Biológicos/imunologia , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/imunologia , Humanos , Interleucina-12/imunologia , Interleucina-17/imunologia , Interleucina-23/imunologia , Psoríase/imunologia , Psoríase/patologia , Índice de Gravidade de Doença
7.
Nihon Yakurigaku Zasshi ; 154(2): 66-71, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31406045

RESUMO

Cytokine signal is essential for the biological function including development, maintenance of homeostasis and progression of disease. There are growing evidences that signaling via pro-inflammatory cytokines underlie a variety of immunological diseases such as psoriasis, atopic dermatitis, inflammatory bowel disease, and metabolic syndromes, in which cytokine signals are known as a potential therapeutic target of antibody drugs. In contrast, anti-inflammatory cytokines, which is represented by IL-10, largely contribute to suppression of inflammation and restoration of injured tissues. IL-19 is a member of IL-10 cytokine family, which comprises IL-20 cytokine subfamily with IL-20, IL-22, IL-24, and IL-26. IL-19 is produced by myeloid and epithelial cells with stimulation of bacterial components and cytokines. Although IL-19 has been originally recognized as a potential Th2-related cytokine, in recent researches, it has been reported that this cytokine upregulates Th17 response to reflect and promote progression of Th17-related disease including psoriasis. On the other hand, IL-19 has anti-inflammatory effects on inflammatory diseases such as infectious skin disease, inflammatory bowel disease, and cardiovascular disease. Therefore, IL-19 may exert pleiotropic effects dependent on the pathological mechanism of inflammatory diseases. In this review, we summarize recent studies about IL-19 and introduce the pathophysiological and therapeutic role of IL-19 in inflammatory diseases.


Assuntos
Interleucinas/imunologia , Psoríase/imunologia , Citocinas/imunologia , Humanos , Inflamação/imunologia , Células Th17/imunologia
8.
J Dermatol ; 46(10): 886-897, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31418479

RESUMO

Patients with dermatomyositis positive for anti-aminoacyl tRNA synthetase (ARS) antibodies, also known as antisynthetase syndrome (ASS), frequently present with mechanic's hand and interstitial lung disease (ILD). We first screened the antibody profiles of 59 patients with dermatomyositis, and then examined the cutaneous, muscular and pulmonary manifestations characteristic for patients with ASS. The anti-ARS antibodies Jo-1, PL-7, PL-12, EJ and KS, along with antibodies to TIF1-γ, MDA5 and Mi-2, were examined. Among the 59 patients, 20, 21, 15 and three patients were classified into the ASS, non-ASS, myositis-specific antibody-negative and unknown groups, respectively. Five of 16 patients (31%) with ASS had six relatives with a history of collagen diseases, within the second degree of relationship, including two cases of dermatomyositis (vs the non-ASS group, P = 0.018). Patients with ASS more frequently presented with fever and arthralgia, and had elevated levels of C-reactive protein. Nine of the 11 finger lesions (82%) clinically diagnosed as mechanic's hands showed a psoriasiform tissue reaction. ILD was observed in 19 of 20 patients (95%) with ASS, and eight of 21 patients (38%) in the non-ASS group, in which six patients possessed anti-MDA5 antibody. Patients with ASS showed higher serum levels of muscle enzymes, and four of 12 patients (33%) had fasciitis-dominant myopathy, while only one of 11 patients (9%) in the non-ASS group had fasciitis-dominant myopathy. Patients with ASS often present with a psoriasiform tissue reaction in the hand lesions and fasciitis-dominant myopathy, and the relatives of those with ASS are at high risk for collagen diseases.


Assuntos
Aminoacil-tRNA Sintetases/imunologia , Autoanticorpos/sangue , Dermatomiosite/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Miosite/diagnóstico , Psoríase/diagnóstico , Adulto , Idoso , Autoanticorpos/imunologia , Dermatomiosite/sangue , Dermatomiosite/imunologia , Feminino , Humanos , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/imunologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Miosite/sangue , Miosite/imunologia , Psoríase/sangue , Psoríase/imunologia , Tomografia Computadorizada por Raios X
9.
Expert Rev Clin Pharmacol ; 12(9): 851-857, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31460804

RESUMO

Introduction: The interleukin (IL)-23 and IL-17 pathway is closely related to the pathogenesis of psoriasis. This pathway is considered to be an important target for treating psoriasis. Risankizumab can selectively inhibit IL-23p19 subunit and for the treatment of psoriasis. This article aims to review risankizumab and provides reference for clinicians. Areas covered: The chemical property, mechanism of action, pharmacokinetics, clinical efficacy, safety of risankizumab was introduced in this paper. A PubMed search using the terms 'risankizumab,' 'IL-23,' 'p19 subunit,' and 'psoriasis,' was performed, and the results were screened for the most relevant English language publications. Expert opinion: Risankizumab is a humanized IgG monoclonal antibody that binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. Clinical trials showed that risankizumab was significantly more effective than ustekinumab. Risankizumab was well tolerated, upper respiratory tract infection was the common adverse reactions. Therefore, the market of risankizumab provides an important therapeutic means for psoriasis.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/farmacologia , Humanos , Interleucina-23/imunologia , Psoríase/imunologia , Psoríase/patologia , Ustekinumab/administração & dosagem
10.
Immunology ; 158(3): 171-193, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31424569

RESUMO

Activated T cells are pathological in various autoimmune and inflammatory diseases including Psoriasis, and also in graft rejection and graft-versus-host-disease. In these pathological conditions, selective silencing of activated T cells through physiological receptors they express remains a clinical challenge. In our previous studies we found that activation of dopamine receptors (DRs) in resting human T cells activates these cells, and induces by itself many beneficial T cell functions. In this study, we found that normal human T cells express all types of DRs, and that expression of D1R, D4R and D5R increases profoundly after T cell receptor (TCR) activation. Interestingly, DR agonists shift the membrane potential (Vm ) of both resting and activated human T cells, and induces instantaneous T cell depolarization within 15 seconds only. Thus, activation of DRs in T cells depolarize these immune cells, alike activation of DRs in neural cells. The skin of Psoriasis patients contains 20-fold more D1R+ T cells than healthy human skin. In line with that, 25-fold more D1R+ T cells are present in Psoriasis humanized mouse model. Highly selective D1-like receptor agonists, primarily Fenoldopam (Corlopam) - a D1-like receptor agonist and a drug used in hypertension, induced the following suppressive effects on activated T cells of Psoriasis patients: reduced chemotactic migration towards the chemokine SDF-1/CXCL12; reduced dramatically the secretion of eight cytokines: tumor necrosis factor-α, interferon-γ, interleukin-1ß (IL-1ß), IL-2, IL-4, IL-6, IL-8 and IL-10; and reduced three T cell activation proteins/markers: CD69, CD28 and IL-2. Next, we invented a novel topical/dermal Fenoldopam formulation, allowing it to be spread on, and providing prolonged and regulated release in, diseased skin. Our novel topical/dermal Fenoldopam: reduced secretion of the eight cytokines by activated human T cells; reduced IL-1ß and IL-6 secretion by human lipopolysaccharide-inflamed skin; eliminated preferentially >90% of live and large/proliferating human T cells. Together, our findings show for the first time that both resting and activated T cells are depolarized instantaneously via DRs, and that targeting D1-like receptors in activated T cells and inflamed human skin by Fenoldopam, in Psoriasis, and potentially in other T cell-mediated diseases, could be therapeutic. Validation in vivo is required.


Assuntos
Fenoldopam/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Psoríase/imunologia , Receptores Dopaminérgicos/imunologia , Pele/imunologia , Linfócitos T/imunologia , Adulto , Antígenos CD/imunologia , Antígenos de Diferenciação de Linfócitos T/imunologia , Antígenos CD28/imunologia , Citocinas/imunologia , Feminino , Humanos , Lectinas Tipo C/imunologia , Masculino , Pessoa de Meia-Idade , Psoríase/patologia , Pele/patologia , Linfócitos T/patologia
11.
J Drugs Dermatol ; 18(8): 776-788, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31424708

RESUMO

Psoriasis (PsO) is a common, systemic, chronic inflammatory disease characterized by key clinical symptoms, including itching, pain, and scaling, and is associated with substantial physical, psychosocial, and economic health burdens. Currently, there is no cure for PsO; however, the introduction of biologic therapies has revolutionized the clinical management of patients with PsO by expanding treatment options to include multiple therapies with different mechanisms of action targeting cytokines, including tumor necrosis factor inhibitors (TNFis), interleukin (IL)-17A inhibitors, an IL-12/23 inhibitor, and IL-23 inhibitors. TNFis are historically considered the first-line biologic treatment and the first-generation biologics; however, increased understanding of TNF-α and IL-17 synergistic functions have recently led to evidence that specifically targeting IL-17 may be more likely to improve disease activity than a more general, nonspecific therapy target, such as TNF-α. This review highlights currently available evidence and demonstrates the differences between TNFis and IL-17A inhibitors in patients with PsO with regard to efficacy and safety.


Assuntos
Produtos Biológicos/uso terapêutico , Interleucina-17/antagonistas & inibidores , Psoríase/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Produtos Biológicos/farmacologia , Ensaios Clínicos como Assunto , Humanos , Reação no Local da Injeção/epidemiologia , Reação no Local da Injeção/etiologia , Interleucina-17/imunologia , Psoríase/diagnóstico , Psoríase/imunologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/etiologia , Índice de Gravidade de Doença , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologia
12.
Nat Immunol ; 20(9): 1138-1149, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31427775

RESUMO

Interleukin (IL)-1R3 is the co-receptor in three signaling pathways that involve six cytokines of the IL-1 family (IL-1α, IL-1ß, IL-33, IL-36α, IL-36ß and IL-36γ). In many diseases, multiple cytokines contribute to disease pathogenesis. For example, in asthma, both IL-33 and IL-1 are of major importance, as are IL-36 and IL-1 in psoriasis. We developed a blocking monoclonal antibody (mAb) to human IL-1R3 (MAB-hR3) and demonstrate here that this antibody specifically inhibits signaling via IL-1, IL-33 and IL-36 in vitro. Also, in three distinct in vivo models of disease (crystal-induced peritonitis, allergic airway inflammation and psoriasis), we found that targeting IL-1R3 with a single mAb to mouse IL-1R3 (MAB-mR3) significantly attenuated heterogeneous cytokine-driven inflammation and disease severity. We conclude that in diseases driven by multiple cytokines, a single antagonistic agent such as a mAb to IL-1R3 is a therapeutic option with considerable translational benefit.


Assuntos
Anticorpos Bloqueadores/farmacologia , Anticorpos Monoclonais/farmacologia , Proteína Acessória do Receptor de Interleucina-1/antagonistas & inibidores , Peritonite/imunologia , Pneumonia/imunologia , Psoríase/imunologia , Células A549 , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Células HEK293 , Humanos , Imiquimode/toxicidade , Inflamação/patologia , Interleucina-1/imunologia , Proteína Acessória do Receptor de Interleucina-1/imunologia , Interleucina-1beta/imunologia , Interleucina-33/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina/toxicidade , Peritonite/tratamento farmacológico , Peritonite/patologia , Pneumonia/tratamento farmacológico , Pneumonia/patologia , Psoríase/tratamento farmacológico , Psoríase/patologia , Transdução de Sinais/imunologia , Ácido Úrico/toxicidade
13.
J Dermatol Sci ; 95(3): 90-98, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31362906

RESUMO

BACKGROUND: Psoriasis is a chronic inflammatory skin disease. Anti-TNFα, IL-17A and IL-23p19 antibodies are effective for psoriasis. However, the contribution of regulatory T cells (Treg) in their effectiveness remains to be elucidated. OBJECTIVE: We investigated the effects of TNFα, IL-17A and IL-23p19 inhibition on Tregs in imiquimod-induced psoriasiform dermatitis. METHODS: Psoriasiform dermatitis was induced by imiquimod application on murine shaved back skin for six days. Mice were treated with anti-TNFα, IL-17A or IL-23p19 monoclonal antibodies every other day from one day before imiquimod application. RESULTS: Administration of anti-TNFα, IL-17A or IL-23p19 antibodies improved the clinical score and downregulated Th17-related cytokines and chemokines, while IL-23p19 antibodies upregulated IL-10 mRNA expression. Anti-IL-17A or IL-23p19 antibody-treated imiquimod-applied mice showed a significant increase in the number of Foxp3+ IL-10+ Tregs. Recipient mice adoptively transferred with Tregs derived from donor mice treated with antibodies demonstrated clinical and pathological improvement in imiquimod-induced psoriasiform dermatitis. Anti-IL-17A or IL-23p19 antibody-induced Tregs significantly increased the number of Foxp3+ cells and IL-10 expression in imiquimod-induced psoriasiform dermatitis in recipient mice but anti-TNFα antibody-induced Tregs did not. CONCLUSION: Anti-IL-17A or IL-23p19 antibody inhibits the IL-17/IL-23 signaling pathway, and induces expansion of Tregs and their suppressive capacity in imiquimod-induced psoriasiform dermatitis.


Assuntos
Anticorpos Monoclonais/farmacologia , Interleucina-17/antagonistas & inibidores , Subunidade p19 da Interleucina-23/antagonistas & inibidores , Psoríase/tratamento farmacológico , Linfócitos T Reguladores/efeitos dos fármacos , Transferência Adotiva , Animais , Anticorpos Monoclonais/uso terapêutico , Modelos Animais de Doenças , Feminino , Humanos , Imiquimode/administração & dosagem , Imiquimode/imunologia , Interleucina-17/metabolismo , Subunidade p19 da Interleucina-23/metabolismo , Camundongos , Psoríase/imunologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Pele , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/transplante , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo
14.
Eur J Dermatol ; 29(3): 302-314, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31389789

RESUMO

The effect and safety of monoclonal antibodies (mAbs) targeting the interleukin-23 (IL-23) p19 subunit for treatment of psoriasis has not previously been systematically evaluated. To perform a systematic review and meta-analysis of randomized clinical trials (RCTs) (including Phase I-III trials) to evaluate the efficacy and safety of these mAbs for treatment of psoriasis. The databases of PubMed, Baidu Scholar, and Cochrane Library of Clinical Trials were searched from inception of the databases to January 1st, 2018. A systematic review and meta-analysis was conducted using Review Manager Software version 5.3 (RevMan 5.3). Nine RCTs with a total of 2,478 subjects met our inclusion criteria. A significant increase in PASI 75 (RR: 11.65; 95% CI: 9.01-15.06), PASI 90 (RR: 21.74; 95% CI: 14.28-33.10), PASI 100 (RR: 31.56; 95% CI: 14.66-67.96), PGA 0/1 (OR: 23.21; 95% CI: 14.61-36.89), and DLQI 0/1 (RR: 10.29; 95% CI: 7.52-14.09) was identified for anti-IL-23p19 mAb vs. placebo, and PASI 75 (RR: 1.25; 95% CI: 1.18-1.32), PASI 90 (OR: 2.56; 95% CI: 2.13-3.09), PASI 100 (OR: 2.38, 95% CI: 1.89-2.99), and DLQI 0/1 (RR: 1.33; 95% CI: 1.20-1.47) vs. tumour necrosis factor (TNF) antagonists for the treatment of psoriasis. Furthermore, there was no significant difference in adverse events between placebo and TNF antagonists. Anti-IL-23p19 mAbs are effective with acceptable safety as therapy for psoriasis, and may be superior to TNF antagonists. More RCTs with a larger sample size are required to verify the current findings.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Subunidade p19 da Interleucina-23/imunologia , Terapia de Alvo Molecular/métodos , Psoríase/tratamento farmacológico , Feminino , Humanos , Masculino , Segurança do Paciente , Psoríase/imunologia , Psoríase/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
16.
Int J Mol Sci ; 20(13)2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284527

RESUMO

Psoriasis is an immune-mediated inflammatory skin disease that involves mainly T helper (Th)17, Th1 and Th22 lymphocytes, which cause hyper-proliferation of the epidermis with aberrant differentiation of keratinocytes, and local production of chemokines and cytokines. These fuel a self-amplifying loop where these products act on T cells to perpetuate cutaneous inflammatory processes. Among the various inflammatory mediators involved, interleukin (IL)-36 cytokines are important for the recruitment and activation of neutrophils and Th17 cells in psoriatic skin. In particular, IL-36s induce chemokines and cytokines interfere with differentiation/cornification programs in the epidermis, as well as promote pathological angiogenesis and endothelial cell activation. IL-36 cytokines belong to the IL-1 family, and comprise IL-36α, IL-36ß, and IL-36γ agonists as well as IL-36 receptor antagonist and IL-38 antagonists. IL-36 cytokines are up-regulated in psoriatic epidermis, and their expression is strongly induced by TNF-α and IL-17. Contrarily, IL-38 antagonist is downregulated, and its impaired expression may be relevant to the dysregulated inflammatory processes induced by IL-36. Here, we discuss on the pathogenic mechanisms leading to the altered balance of IL-36 agonists/antagonists and the significance of this dysregulation in psoriasis. Collection of the information will provide a theoretical basis for the development of novel therapeutic strategies based on IL-36 agonist/antagonist manipulation in psoriasis.


Assuntos
Interleucina-1/metabolismo , Psoríase/metabolismo , Receptores de Interleucina/metabolismo , Animais , Modelos Animais de Doenças , Humanos , Psoríase/imunologia , Psoríase/patologia , Transdução de Sinais , Pele/patologia
17.
J Ethnopharmacol ; 242: 112073, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31288049

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rosin, an exudate of conifer trees such as Pinus masscnlana (Pinaceae), has been used to treat psoriasis for nearly two thousand years in China despite its so far undefined pharmacology. Unfortunately, the rosin intoxication is noted from time to time, but the water-boiled rosin (WBR) has been documented to be safer. This study was performed to evaluate the in vivo anti-psoriasis efficacy of WBR. MATERIALS AND METHODS: The main phytochemicals in WBR were quantified by high performance liquid chromatography (HPLC). WBR was evaluated in the imiquimod-induced psoriasis-like inflammation mouse model for its anti-psoriasis effect at 130, 260, and 390 mg/kg, which were set according to the dose used for patients. Through a combination of q-PCR, flow cytometry, and histopathological and immunohistochemical (IHC) analysis, the in vivo efficacy was assessed in terms of the psoriasis area severity index (PASI), epidermal keratinocyte proliferation, Th1 and Th17 cell numbers in spleen, and mRNA expressions of inflammatory cytokines. RESULT: Oral administration of WBR ameliorates the psoriasis-like dermatitis in the imiquimod-generated mouse model. In particular, WBR given at 260 or 390 mg/kg significantly restores the normal keratinization of dorsal lesion if compared with the untreated psoriatic mice. Such an effect was addressed to correlate to the Th1/Th17 cell reduction in spleen and the suppressed expression of IL-17A, IL-17F, IL-22, IL-23, TNF-α, K17, and proliferating cell nuclear antigen (PCNA) after the WBR administration. CONCLUSION: WBR is effective in the imiquimod-induced psoriasis-like inflammation mouse model with the efficacy arising from its proliferation inhibition of Th1/Th17 cells and epidermal keratinocytes via the down-regulation of the relevant inflammatory cytokines such as IL-23, IL-17A, and IL-17F. Collectively, WBR harvested and processed in the traditional manner is an efficacious psoriasis-treating agent.


Assuntos
Anti-Inflamatórios/uso terapêutico , Psoríase/tratamento farmacológico , Resinas Vegetais/uso terapêutico , /análise , /uso terapêutico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Proliferação de Células/efeitos dos fármacos , Citocinas/genética , Citocinas/imunologia , Feminino , Imiquimode , Camundongos Endogâmicos BALB C , Psoríase/induzido quimicamente , Psoríase/imunologia , Psoríase/patologia , Resinas Vegetais/química , Resinas Vegetais/farmacologia , Pele/efeitos dos fármacos , Pele/patologia , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Água/química
18.
Nat Immunol ; 20(8): 992-1003, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31263279

RESUMO

Here we identify a group 2 innate lymphoid cell (ILC2) subpopulation that can convert into interleukin-17 (IL-17)-producing NKp44- ILC3-like cells. c-Kit and CCR6 define this ILC2 subpopulation that exhibits ILC3 features, including RORγt, enabling the conversion into IL-17-producing cells in response to IL-1ß and IL-23. We also report a role for transforming growth factor-ß in promoting the conversion of c-Kit- ILC2s into RORγt-expressing cells by inducing the upregulation of IL23R, CCR6 and KIT messenger RNA in these cells. This switch was dependent on RORγt and the downregulation of GATA-3. IL-4 was able to reverse this event, supporting a role for this cytokine in maintaining ILC2 identity. Notably, this plasticity has physiological relevance because a subset of RORγt+ ILC2s express the skin-homing receptor CCR10, and the frequencies of IL-17-producing ILC3s are increased at the expense of ILC2s within the lesional skin of patients with psoriasis.


Assuntos
Interleucina-17/imunologia , Linfócitos/imunologia , Psoríase/patologia , Pele/patologia , Células Cultivadas , Humanos , Interleucina-1beta/imunologia , Subunidade p19 da Interleucina-23/imunologia , Interleucina-4/imunologia , Linfócitos/citologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Psoríase/imunologia , Receptores CCR10/metabolismo , Pele/imunologia , Fator de Crescimento Transformador beta/metabolismo
19.
Molecules ; 24(11)2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31181689

RESUMO

BACKGROUND: Psoriasis is a chronic, immune-mediated inflammatory skin disease, and the inflammatory response plays an important role in its development and progression. Datura metel L. is a traditional Chinese medicine that exhibited a significant therapeutic effect on psoriasis in our previous study due to its remarkable anti-inflammatory effect. Meanwhile, the mechanism underlying its effects on psoriasis is still unclear. METHODS: An imiquimod-induced psoriasis-like dermatitis mouse model was constructed to evaluate the protective effect of the effective part of Datura metel L. (EPD), which was verified by evaluations of the Psoriasis Area and Severity Index (PASI) score. Hematoxylin and eosin (H&E) staining, immunohistochemical examination, enzyme-linked immunosorbent assay (ELISA), and Western blot were used to measure the inflammatory cytokines and the protein expression associated with the Toll-like receptor 7- myeloid differentiation primary response gene 88-nuclear Factor-κB-nucleotide-binding oligomerization domain (Nod)-like receptor family pyrin domain-containing 3 (TLR7/8-MyD88-NF-κB-NLRP3) inflammasome pathway. RESULTS: EPD significantly decreased the PASI, reduced epidermal thickness, and decreased the proliferation and differentiation of epidermal cells in psoriasis-like dermatitis C57BL/6 mice induced by imiquimod (IMQ). Furthermore, EPD reduced the infiltration of CD3+ cells to psoriatic lesions, as well as ameliorated the elevations of intercellular adhesion molecule 1 (ICAM-1) and inhibited the production of imiquimod-induced inflammatory cytokines, including IL-1ß, IL-2, IL-6, IL-10, IL-12, IL-17, IL-22, IL-23, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP-1), and interferon-γ (IFN-γ). Besides, EPD decreased the imiquimod-induced expression levels of TLR7, TLR8, TRAF6, MyD88, p-IKKα, p-IKBα, p-NF-κB, NLRP3, apoptosis-associated speck-like protein contained a caspase recruitment domain (ASC), cysteinyl aspartate specific proteinase 1 (caspase-1), and IL-1ß. CONCLUSION: This study demonstrated that EPD exhibited a protective effect on an imiquimod-induced psoriasis mice model by inhibiting the inflammatory response, which might be ascribed to the inhibition of the TLR7/8-MyD88-NF-κb-NLRP3 inflammasome pathway.


Assuntos
Citocinas/metabolismo , Datura metel/química , Medicamentos de Ervas Chinesas/administração & dosagem , Imiquimode/efeitos adversos , Psoríase/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Regulação para Baixo , Medicamentos de Ervas Chinesas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Psoríase/induzido quimicamente , Psoríase/imunologia , Receptor 7 Toll-Like/metabolismo , Receptor 8 Toll-Like/metabolismo
20.
Int Immunopharmacol ; 73: 442-450, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31154289

RESUMO

Etanercept has greatly improved management considerably. However, the efficacy and safety of combination therapy with methotrexate and the mechanism of action are not known. We aimed to describe the use of combined therapy of etanercept and methotrexate against moderate-to-severe plaque psoriasis in a Chinese population. We also wished to study the changes in expression of pro-inflammatory factors in peripheral blood mononuclear cells (PBMCs) and serum after the treatment to ascertain the mechanism of action. Thirty patients with moderate-to-severe plaque psoriasis were assigned into a monotherapy group and combination group randomly and equally. All patients received etanercept (50 mg, s.c., weekly), whereas patients in the combination group also received oral methotrexate (7.5-15 mg, p.o., weekly). Serum levels of interleukin (IL)-17A, IL-23, tumor necrosis factor (TNF)-α and their mRNA expressions in PBMCs were measured by ELISA and qRT-PCR. In the monotherapy group, Psoriasis Area and Severity Index (PASI) 50/75/90 responses were achieved by 86.7/66.7/40% after 24 weeks of treatment whereas, in the combination group, they were achieved by 93.3/80/60%, respectively. Although the overall prevalence of adverse effects (AEs) was higher in the combination group (60%) than in the monotherapy group (33.3%), the AEs were mild to moderate. The serum levels of IL-17A, IL-23, TNF-α, IL-33 and their mRNA expression in the PBMCs of the two groups were significantly higher than those of healthy controls (P < 0.05). Compared with the monotherapy group, serum levels of IL-17A, IL-23, TNF-α and their mRNA expression in PBMCs were decreased significantly in the combination group (P < 0.05). These data suggest that the efficacy of etanercept could be improved upon combination with methotrexate in the treatment of moderate-to-severe plaque psoriasis without increasing the risk of serious AEs. The mechanism of action might be associated with down-regulation of IL-17A, IL-23, and TNF-α.


Assuntos
Etanercepte/uso terapêutico , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Psoríase/tratamento farmacológico , Adulto , Idoso , Citocinas/imunologia , Quimioterapia Combinada , Feminino , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Psoríase/imunologia , Índice de Gravidade de Doença , Resultado do Tratamento
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