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Th17 methotrexate

Wei Zhong, Ling Zhao, Tao Liu, Zhenyu Jiang
T cells are key players in immune-mediated rheumatoid arthritis (RA). We previously reported that interleukin (IL)-22(+)CD4(+)T helper (IL-22(+) Th) cells and IL-22 critically control the pathogenesis of RA. Here we monitored circulating levels of different IL-22(+) Th cell subsets and measured plasma levels of IL-22, IL-17, and interferon (IFN)-γ in 60 patients with active RA following 12-week combination methotrexate (MTX) and leflunomide (LEF) therapy (MTX+LEF) and 20 healthy individuals. We found the frequencies of circulating IFN-γ(-)IL-17(-)IL-22(+) (Th22), IFN-γ(-)IL-17(+) (total Th17), IFN-γ(+)IL-17(-)IL-22(+) (IL-22(+)Th1) cells, and IFN-γ(-)IL-17(+)IL-22(+) (IL-22(+)Th17) cells, as well as the plasma levels of IL-22, IL-17 and IFN-γ to be significantly reduced in RA patients that responded to treatment, but not in non-responders...
January 24, 2017: Scientific Reports
Christian Pagnoux
Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are small-vessel vasculitides that include granulomatosis with polyangiitis (formerly Wegener's granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Renal-limited ANCA-associated vasculitides can be considered the fourth entity. Despite their rarity and still unknown cause(s), research pertaining to ANCA-associated vasculitides has been very active over the past decades. The pathogenic role of antimyeloperoxidase ANCA (MPO-ANCA) has been supported using several animal models, but that of antiproteinase 3 ANCA (PR3-ANCA) has not been as strongly demonstrated...
September 2016: European Journal of Rheumatology
Songsong Li, Zhenzhou Wu, Ling Li, Xuehua Liu
BACKGROUND The aim of this study was to investigate the protective effect of interleukin-6 (IL-6) receptor antagonist tocilizumab (TCZ) on rheumatoid arthritis (RA) and its related mechanism. MATERIAL AND METHODS Thirty RA patients receiving long-term methotrexate therapy at moderate and severe active stages were selected and treated with TCZ 8 mg/kg/time iv gtt intravenously guttae every 4 weeks. Peripheral blood was extracted before and 24 weeks after TCZ treatment. Peripheral blood mononuclear cells (PBMC) were collected by density gradient centrifugation...
June 20, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Sebastian Volc, Kamran Ghoreschi
Over the past 15 years, the spectrum of systemic antipsoriatic treatments has dramatically expanded. Until the end of the last millennium, systemic therapy had been restricted to four oral agents: methotrexate, cyclosporine, acitretin, and fumaric acid esters. Today, there are additionally seven biologics and one new oral antipsoriatic drug, as well as the first available biosimilars. Six more biologics with novel target structures and at least four biosimilars are currently being developed (phase III). This progress has been based on new insights into the pathogenesis of psoriasis, in which tumor necrosis factor and especially Th17 immune responses with their associated cytokines interleukin 23 and 17 play a key role...
June 2016: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
Shigeru Kotake, Yuki Nanke, Toru Yago, Manabu Kawamoto, Tsuyoshi Kobashigawa, Hisashi Yamanaka
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone with elevated levels of proinflammatory cytokines. It has been reported that IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. It remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we tried to identify Th17 cells, Th1 cells, and Th17 cell-derived Th1 cells (CD161(+)Th1 cells) in the peripheral blood of early-onset RA patients...
2016: BioMed Research International
Yaxiong Deng, Christopher Chang, Qianjin Lu
Psoriasis is a chronic inflammatory autoimmune disease characterized by an excessively aberrant hyperproliferation of keratinocytes. The pathogenesis of psoriasis is complex and the exact mechanism remains elusive. However, psoriasis is thought to result from a combination of genetic, epigenetic, and environmental influences. Recent studies have identified that epigenetic factors including dysregulated DNA methylation levels, abnormal histone modification and microRNAs expressions are involved in the development of psoriasis...
June 2016: Clinical Reviews in Allergy & Immunology
Hongyan Wen, Jing Luo, Xiaoying Zhang, Chen Zhang, Xiangcong Zhao, Xin Wang, Xiaofeng Li
OBJECTIVE: To investigate the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)₂D₃] on T helper cell type 17 (Th17) cytokines and therapeutic mechanism in patients with rheumatoid arthritis (RA). METHODS: Peripheral blood mononuclear cells (PBMCs) from healthy donors and RA patients were collected. The PBMCs were stimulated with anti-CD3/anti-CD28 monoclonal antibodies in the absence or presence of 1,25(OH)₂D₃and methotrexate (MTX). After co-culture, the serum levels of Th17 cytokines interleukin (IL)-17, IL-6, tumour necrosis factor alpha (TNFα) were analyzed by cytometric bead array (CBA)...
April 2015: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
Jun-Eui Park, Jinah Jang, Ji-Hye Choi, Mi-Sun Kang, Yun-Ju Woo, Young-Rim Seong, Chan-Bum Choi, Hye-Soon Lee, Sang-Cheol Bae, Yong-Soo Bae
We have previously demonstrated that semimature dendritic cell- (smDC-) based immunotherapy is effective for the treatment of collagen-induced arthritis (CIA) prior to disease onset. In the present study, we examined the efficacy of combination therapy with smDCs and methotrexate (MTX) in advanced CIA with a score of 2-3. Combination therapy with low-dose MTX and type II collagen- (CII-) pulsed smDCs (CII-smDCs) was more effective in inhibiting disease progression than high or low-dose MTX alone or a combination of high dose MTX and CII-smDCs...
2015: Journal of Immunology Research
Yoshiya Tanaka
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovial inflammation and joint destruction. However, the combined use of synthetic disease-modifying anti-rheumatic drug (DMARD) such as methotrexate and a biological DMARD targeting tumour necrosis factor (TNF) has revolutionized treatment of RA. Clinical remission is a realistic target to treat and the maintenance of remission has produced significant improvements in structural and function outcomes. However, biological DMARDs are limited to intravenous or subcutaneous uses and orally available small but strong products have been developed...
September 2015: Journal of Biochemistry
Eun Wha Choi, Il Seob Shin, Ji Woo Song, MinJae Lee, Tae Won Yun, Jehoon Yang, Kyu-Sil Choi, Sung-Joo Kim
CTLA4Ig has therapeutic potential for rheumatoid arthritis patients unresponsive to methotrexate (MTX) or TNF-α blockers. However, recombinant CTLA4Ig proteins are short acting and expensive. Adipose tissue-derived mesenchymal stem cells (ASCs) present an ideal stem cell source for practical regenerative medicine due to their abundant availability and their beneficial properties including immunomodulation, homing activity, paracrine effects, and differentiation ability. Therefore, we aimed to determine whether CTLA4Ig and human ASCs show synergistic effects on immunomodulation and clinical improvement of sustained severe rheumatoid arthritis in a mouse model...
2016: Cell Transplantation
Ari M Goldminz, Mayte Suárez-Fariñas, Andrew C Wang, Nicole Dumont, James G Krueger, Alice B Gottlieb
IMPORTANCE: Methotrexate is a first-line systemic agent for treating of psoriasis, although its onset of effects is slower and overall it is less effective than tumor necrosis factor blockers. OBJECTIVE: To differentiate the response of psoriatic disease to adalimumab and methotrexate sodium. DESIGN, SETTING, AND PARTICIPANTS: Single-center, randomized, assessor-blind, 2-arm clinical trial of 30 patients from the outpatient dermatology center of Tufts Medical Center, enrolled from August 18, 2009, to October 11, 2011...
August 2015: JAMA Dermatology
Zhao Xiao, Long Juan, Yun Song, Zhang Zhijian, Jin Jing, Yu Kun, Hao Yuna, Dai Dongfa, Ding Lili, Tan Liuxin, Liang Fei, Liu Nan, Yuan Fang, Sun Yuying, Xi Yongzhi
A major challenge in the development of effective therapies for rheumatoid arthritis (RA) is finding a method for the specific inhibition of the inflammatory disease processes without the induction of generalized immunosuppression. Of note, the development of therapeutic DNA vaccines and boosters that may restore immunological tolerance remains a high priority. pcDNA-CCOL2A1 is a therapeutic DNA vaccine encoding chicken type II collagen(CCII). This vaccine was developed by our laboratory and has been shown to exhibit efficacy comparable to that of the current "gold standard" treatment, methotrexate (MTX)...
2015: Human Vaccines & Immunotherapeutics
Agata Kosmaczewska, Lidia Ciszak, Jerzy Swierkot, Aleksandra Szteblich, Katarzyna Kosciow, Irena Frydecka
Interleukin-2 (IL-2) has been suggested to control Treg/Th17 balance. Recently, we reported a relationship of rheumatoid arthritis (RA) activity/progression with irreversible systemic Treg and Th1 defects including serum IL-2 shortage. Herein, we explore the role of in vitro stimulation with rIL-2 in the observed immune alterations reversal. Patients with stable or progressive RA were assigned to methotrexate (MTX) group or to TNF-alpha inhibitors (iTNF) group, respectively. Flow cytometric analyses were performed before and after 6 months of treatment...
April 2015: Inflammation
Dashlkhumbe Byamba, Do Young Kim, Dae-Suk Kim, Tae-Gyun Kim, Hyunjoong Jee, Sung Hee Kim, Tae-Yoon Park, Sang-Hwa Yang, Sang-Kyou Lee, Min-Geol Lee
Accumulating evidence has shown that the Toll-like receptor 7 agonist imiquimod (IMQ) induces psoriasiform skin inflammation in mice and that this inflammation is dependent on the IL-23/IL-17 axis. Moreover, it has been demonstrated that the main source of IL-17 is not Th17 but is dermal gamma delta (γδ) T cells in mouse psoriasiform skin. Recent advances in the understanding of immunopathogenesis of psoriasis led to an alteration in the treatment paradigm to the use of highly efficacious biologics. However, their high cost impedes the extensive use of these agents...
July 2014: Experimental Dermatology
G Guggino, A Giardina, A Ferrante, G Giardina, C Schinocca, G Sireci, F Dieli, F Ciccia, G Triolo
The aim of our study was to evaluate methotrexate (MTX) and methylprednisolone (MP) effect on peripheral Th17 and Treg subsets in patients with rheumatoid arthritis (RA). We enrolled 15 patients (10 early RA and 5 long-standing disease) with active RA and 10 age-matched healthy donors as controls. Frequencies of Th17 and Treg were quantified using flow cytometry before and after in vitro addition of MTX, MP or both drugs. Our results showed a reduction in the overall Th17 population followed by an increase in Th17 IL-10(+) and Treg, after in vitro treatment of PBMCs with the drugs in patients with early RA...
January 2015: Rheumatology International
M de la Brassinne, Af Nikkels
The treatment of psoriasis is mainly based on anti-inflammatory and/or anti-hyperproliferative agents. The topical steroids appeared in the fifties and were the first therapeutic breakthrough for psoriasis, followed by methotrexate and phototherapy in the sixties, photochemotherapy (PUVA) in the seventies and acitretin and cyclosporine in the eighties. The targeted biologic therapies represent a whole new era of therapeutic possibilities with a highly beneficial safety record. The choice of treatment depends on a large series of factors, including the type and extend of the psoriasis, the patient's preferences, co-medications, comorbidities and drug tolerance...
November 2013: Acta Clinica Belgica
Joshua E Weitz, Christopher T Ritchlin
INTRODUCTION: Psoriatic arthritis (PsA) is a clinically diverse inflammatory arthritis that can affect peripheral joints and the axial skeleton. About 25% of psoriasis patients develop PsA and many suffer from reduced function and quality of life. Anti-TNF agents have emerged as a pivotal treatment for many patients but the lack of alternative biologics for those who become unresponsive and or tolerate these medications remain a major unmet need. Recently, ustekinumab (UST) an agent that targets the 12 - 23/Th17 pathway was approved by the FDA for the treatment of active PsA...
April 2014: Expert Opinion on Biological Therapy
Tarek Mahmoud Elghandour, Sahar El Sayed Youssef, Dalia Gamal Aly, Mohamed Said Abd Elhameed, Mehrevan Mostafa Abdel Moneim
Background. There is raised interest in the involvement of interleukin-(IL-)23/T-helper 17 cells (Th17) axis in the pathogenesis of psoriasis. Objectives. To compare the effect of narrow band ultraviolet B (NB-UVB) and methotrexate (MTX) therapy on serum levels of IL-17 and IL-23 in psoriatic patients. Methods. Thirty patients with severe plaque psoriasis were included: 15 patients received NB-UVB three times weekly (group I) and 15 patients received MTX 0.3 mg/kg per week (group II), both for 8 weeks. Before and after treatment, serum levels of IL-17 and IL-23 were investigated by ELISA technique and psoriasis area and severity index (PASI) was calculated...
2013: Dermatology Research and Practice
E Tamilselvi, D Haripriya, M Hemamalini, G Pushpa, S Swapna
Interleukin-1 plays a key role in inflammation and keratinocyte activation. It is an important mediator in the initiation and maintenance of psoriatic plaques and may represent an attractive therapeutic target. The aim of this study is to evaluate the effect of Methotrexate (MTX) on IL-1 α and IL-1 β levels in both plasma and skin biopsy of patients with psoriasis and to investigate their association with clinical disease activity. Forty-five control subjects and 58 patients with psoriasis were recruited for this study...
December 2013: Scandinavian Journal of Immunology
Paulina Chalan, Bart-Jan Kroesen, Kornelis S M van der Geest, Minke G Huitema, Wayel H Abdulahad, Johan Bijzet, Elisabeth Brouwer, Annemieke M H Boots
Improved understanding of the immune events discriminating between seropositive arthralgia and clinical synovitis is of key importance in rheumatology research. Ample evidence suggests a role for Th17 cells in rheumatoid arthritis. We hypothesized that CD4+CD161+ cells representing Th17 lineage cells may be modulated prior to or after development of clinical synovitis. Therefore, in a cross-sectional study, we investigated the occurrence of CD4+CD161+ T-cells in seropositive arthralgia patients who are at risk for developing rheumatoid arthritis and in newly diagnosed rheumatoid arthritis patients...
2013: PloS One
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