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Il-23 and psoriasis

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https://www.readbyqxmd.com/read/28319618/new-biologics-in-psoriasis-an-update-on-il-23-and-il-17-inhibitors
#1
Joanna Dong, Gary Goldenberg
As immune-related pathways involved in the pathogenesis of psoriasis are elucidated, new biologic treatments targeting these steps of the psoriatic immune cascade are developed. In this article, we review the literature on IL-23 and IL-17 inhibitors in the pipeline for use in moderate to severe psoriasis. Numerous pipeline biologic therapies, including risankizumab, guselkumab, tildrakizumab, ixekizumab, and brodalumab, are being investigated in phase 2 and 3 studies to establish the efficacy and safety of these new agents...
February 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/28300862/reversible-posterior-leukoencephalopathy-syndrome-rpls-in-a-psoriasis-patient-treated-with-ustekinumab
#2
Lauren Dickson, Alan Menter
The use of monoclonal antibodies against interleukin (IL)-12 and -23, such as ustekinumab, has considerably reduced the disease burden in many patients with moderate to severe psoriasis. Reversible posterior leukoencephalopathy syndrome (RPLS) is a neurologic disorder that has been documented with increased frequency with the use of systemic and biologic agents. We report a case of a 58-year-old man with psoriasis who presented with confusion and memory difficulties after being on treatment with ustekinumab for over six years...
February 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28299442/interleukin-il-18-cooperatively-with-il-23-induces-prominent-inflammation-and-enhances-psoriasis-like-epidermal-hyperplasia
#3
Noriko Shimoura, Hiroshi Nagai, Susumu Fujiwara, Haruki Jimbo, Takayuki Yoshimoto, Chikako Nishigori
The interleukin (IL)-23/IL-17 axis is strongly implicated in the pathogenesis of psoriasis. Previous studies showed that IL-18 was elevated in early active and progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index. However, the mechanism whereby IL-18 affects disease severity remains unknown. In this study, we investigated the effects of IL-18 on a psoriasis-like skin inflammation model induced by recombinant mouse IL-23. We found that IL-18, cooperatively with IL-23, induced prominent inflammation and enhanced psoriasis-like epidermal hyperplasia...
March 15, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28285360/kynurenic-acid-downregulates-il-17-1l-23-axis-in-vitro
#4
Sanam Salimi Elizei, Malihe-Sadat Poormasjedi-Meibod, Xia Wang, Maryam Kheirandish, Aziz Ghahary
Exploring the function of interleukin (IL) 17 and related cytokine interactions have been proven useful toward understanding the role of inflammation in autoimmune diseases. Production of the inflammatory cytokine IL-23 by dendritic cells (DC's) has been shown to promote IL-17 expression by Th17 cells. It is well established that Th17 cells play an important role in several autoimmune diseases including psoriasis and alopecia. Our recent investigations have suggested that Kynurenine-rich environment can shift a pro-inflammatory response to an anti-inflammatory response, as is the case in the presence of the enzyme Indoleamine 2,3 dioxygenase (IDO), the rate-limiting enzyme in tryptophan degradation and Kynurenine (Kyn) production...
March 11, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28276258/an-interleukin-12-b-single-nucleotide-polymorphism-increases-il-12p40-production-and-is-associated-with-increased-disease-susceptibility-in-patients-with-relapsing-remitting-multiple-sclerosis
#5
Mohammad Reza Javan, Sarieh Shahraki, Amin Safa, Mohammad Reza Zamani, Arash Salmaninejad, Saeed Aslani
BACKGROUND: Through mounting genetic investigations, it has been established that IL12B and IL23R gene single nucleotide polymorphisms have significant associations with autoimmune diseases including inflammatory bowel disease, psoriasis, and ankylosing spondylitis. IL-12/IL-23 pathway plays a pivotal role in etiopathogenesis of multiple sclerosis (MS), suggested by studies both in patients and animal models. METHODS: In a case-control study, 145 MS patients and 200 healthy subjects were genotyped for polymorphisms in IL12B and IL23R genes using Real-Time PCR allelic discrimination approach...
March 9, 2017: Neurological Research
https://www.readbyqxmd.com/read/28271735/tildrakizumab-for-treating-psoriasis
#6
Marco Galluzzo, S D'Adamio, L Bianchi, M Talamonti
Agents that block inflammatory pathways other than tumor necrosis factor (TNF) have represented new options for treating psoriasis in recent years. IL-23 is involved in regulating Th17 cells and is a potent activator of keratinocyte proliferation. Targeting IL-23p19 alone may be a promising treatment approach in patients with moderate-to-severe chronic plaque psoriasis, with a downregulation of Th17 and Th22 cell responses, while IL-12 blockade is not required to achieve efficacy in these patients. Areas covered: The authors review and provide an update on tildrakizumab, a humanized IgG1 monoclonal antibody that blocks the p19 subunit of IL-23...
March 8, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28266782/systemic-immune-mechanisms-in-atopic-dermatitis-and-psoriasis-with-implications-for-treatment
#7
REVIEW
Emma Guttman-Yassky, James G Krueger, Mark G Lebwohl
Atopic dermatitis (AD) and psoriasis are inflammatory skin diseases that negatively affect patients' quality of life. Although distinctions exist between these diseases, both are characterised by erythematous, thickened epidermal lesions that vary in intensity and affected body surface area. Early models of etiology attributed symptoms of both diseases to cutaneous inflammation at lesion sites, but recent studies have established that activated immune mediators in the circulation drive disease severity. Activation of T helper 2 (Th2) and Th22 cells in the circulation appears to be the principal initiator of acute AD pathology, with the emergence of Th1 and Th17/interleukin (IL)-23 pathway activation marking the transition to a chronic state...
March 7, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28258057/psoriasis-as-a-human-model-of-disease-to-study-inflammatory-atherogenesis
#8
Charlotte L Harrington, Amit K Dey, Raza Yunus, Aditya A Joshi, Nehal N Mehta
Inflammation is known to play a significant role in the process of atherogenesis and cardiovascular disease (CVD). Indeed, patients with chronic inflammatory diseases are at increased risk for cardiovascular events. The mechanisms linking chronic inflammation and CVD however remain poorly understood. Psoriasis, a chronic inflammatory skin disease associated with a greater risk of early cardiovascular events, provides a suitable human model to study the pathophysiology of inflammatory atherogenesis in humans...
March 3, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28224166/routine-laboratory-parameter-dynamics-and-laboratory-adverse-events-in-psoriasis-patients-on-long-term-treatment-with-adalimumab-etanercept-and-ustekinumab
#9
Jochen H Hoffmann, Christian Knoop, Alexander H Enk, Eva N Hadaschik
Only limited data on laboratory parameter dynamics and safety under prolonged biologic treatment in a "real-world" scenario are available for recommendations on screening and monitoring. This study is a retrospective analysis of routine parameter dynamics and laboratory adverse events (LAE) in psoriasis patients on long-term treatment (n = 199) with tumour necrosis factor (TNF)-α-antagonists (adalimumab, etanercept), and the interleukin (IL)12/23-antagonist ustekinumab. Overall, neutrophil (PMN) counts (-11%) and triglycerides (+9%) changed considerably...
February 22, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28168735/does-imiquimod-pretreatment-optimize-308-nm-excimer-laser-uvb-therapy-in-psoriasis-patients
#10
Joselin D Tacastacas, Patricia Oyetakin-White, David C Soler, Andrew Young, Sarah Groft, Kord Honda, Kevin D Cooper, Thomas S McCormick
Psoriasis continues to be a debilitating skin disease affecting 1-3% of the United States population. Although the effectiveness of several current biologic therapies have described this pathology as a IL-23, TNF-α and Th17-mediated disease, less invasive approaches are still in use and in need of refinement. One of these is the usage of narrow band-UVB (NB-UVB) therapy to deplete specifically intra-epidermal CD3(+) , CD4(+) and CD8(+) cells to clear psoriatic plaques. In order to improve NB-UVB therapy, we sought to determine whether skin pre-treatment with the TLR7 agonist imiquimod (IMQ) would help increase the efficiency of the former at resolving psoriatic plaques...
February 7, 2017: Photodermatology, Photoimmunology & Photomedicine
https://www.readbyqxmd.com/read/28165883/the-role-of-il-23-in-the-treatment-of-psoriasis
#11
Lluís Puig
The IL-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis. Human IL-23 is primarily produced by antigen-presenting cells and induces and maintains differentiation of Th17 cells and Th22 cells, a primary cellular source of proinflammatory cytokines such as IL-17 and IL-22, which mediate the epidermal hyperplasia, keratinocyte immune activation and tissue inflammation inherent in psoriasis. Agents that target the p40 subunit common to both IL-12 and IL-23 have shown robust clinical activity, but selectivity for IL-23p19 could offer advantages in efficacy and safety with respect to anti-p40 blockade...
February 6, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28150333/varicella-zoster-virus-meningitis-under-ustekinumab-because-of-plaque-psoriasis
#12
Claudia Stöllberger, Josef Finsterer
Ustekinumab, a monoclonal antibody that binds to the shared p40 subunit of interleukin (IL)-12 and IL-23, is approved in the USA and Europe for moderate to severe plaque psoriasis. There are concerns that biologic treatments like ustekinumab may lead to an increased rate of infections. We report a 77-year-old woman who developed varicella zoster virus meningitis 8 weeks after initiation of ustekinumab therapy because of plaque psoriasis. She presented clinically with sudden onset of fatigue, vertigo, nausea and epileptic seizures...
February 2, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28139054/ustekinumab-for-the-treatment-of-acrodermatitis-continua-of-hallopeau-refractory-to-anti-tnf-agents
#13
Esra Adışen, İlkay Özer, Berkay Temel, Mehmet Ali Gürer
Acrodermatitis continua of Hallopeau (ACH) is a variant of pustular psoriasis that is often very difficult to treat. Almost all anti-psoriatic agents have been used in the treatment of ACH. Ustekinumab, a fully human monoclonal antibody of the IgG1 class, is directed to the shared p40 subunit of cytokines IL-12 and IL-23. Herein, we present our experience of ustekinumab use in a 50-year-old man who was resistant to anti-tumor necrosis factor-α agents. Though initial therapy with ustekinumab achieved a sustained response in our patient, after a seven months of interruption, retreatment resulted in a slower and poorer response than the initial regimen...
January 30, 2017: Dermatologic Therapy
https://www.readbyqxmd.com/read/28122268/interluekin-17a-il17a
#14
REVIEW
Kong Chen, Jay K Kolls
The discovery of the key roles of interleukin-17A (IL-17A) and IL-17A producing cells in inflammation, autoimmune diseases and host defense has led to the experimental targeting of the IL-17A pathway in animal models of diseases as well as in clinical trials in humans. These therapeutic agents include biological products that target IL-17A and IL-23, an upstream regulator of IL-17A production. IL-17A producing T helper cells (Th17 cells) are a distinct lineage from the Th1 and Th2 CD4+ lineages and have been suggested to represent a good drug target in certain inflammatory conditions...
January 22, 2017: Gene
https://www.readbyqxmd.com/read/28122069/interleukin-23-helper-t-cell-17-axis-as-a-treatment-target-for-pityriasis-rubra-pilaris
#15
Laurence Feldmeyer, Alessio Mylonas, Olivier Demaria, Anna Mennella, Nikhil Yawalkar, Emmanuel Laffitte, Daniel Hohl, Michel Gilliet, Curdin Conrad
Importance: Treatment of pityriasis rubra pilaris (PRP) is solely based on its resemblance to psoriasis rather than any knowledge of its pathomechanism. Insight into pathogenic mediators of inflammation is essential for targeted and valid treatment options that could replace previous serendipitous therapeutic approaches in refractory PRP. Objective: To determine whether blockade of the interleukin 23-helper T cell 17 (IL-23-TH17) pathway with ustekinumab represents an efficacious and, based on its proinflammatory cytokine profile, targeted treatment option in PRP...
January 25, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28115058/ccr6-is-dispensable-for-the-development-of-skin-lesions-induced-by-imiquimod-despite-its-effect-on-epidermal-homing-of-il-22-producing-cells
#16
Perrine M Cochez, Camille Michiels, Emilie Hendrickx, Nicolas Dauguet, Guy Warnier, Jean-Christophe Renauld, Laure Dumoutier
Expression of the chemokine receptor Ccr6 is shared by most IL-22 producing cells and Ccr6-deficient mice showed decreased IL-22 production and skin inflammation upon IL-23 intradermal injections. To determine whether this observation might be extended to another psoriasis model, we applied imiquimod on Ccr6-deficient mice. Whereas epidermal IL-22 production was decreased because of a deficient recruitment of γδ T cells in these mice, they were not protected against psoriatic lesions. When primary epidermis or dermis tissue culture cells from non-treated mice were stimulated ex vivo with IL-1α/IL-2/IL-23, we observed that Ccr6 is crucial for Il22 expression from epidermal but not dermal cultures...
January 20, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28109175/langerhans-cell-markers-cd1a-and-cd207-are-the-most-rapidly-responding-genes-in-lesional-psoriatic-skin-following-adalimumab-treatment
#17
L Raaby, C Rosada, A Langkilde, K L Lauridsen, H Vinter, P Ommen, R B Kjellerup, C Johansen, L Iversen
TNFα-, IL-23- and IL-17-targeting drugs are highly effective in the treatment of psoriasis. However, the precise molecular mechanism remains unknown. In psoriatic skin the presence of Langerhans cells (LC) is reduced, but the role of LC is poorly understood. The purpose of this study was to investigate the impact of TNFα and IL-23/IL-17 on the presence of LC in the skin during treatment. Therefore, psoriatic skin was investigated before and after 4 days of adalimumab or ustekinumab treatment. Furthermore, TNFα and IL-17A stimulation was investigated in an ex vivo model of epidermis and dermis from healthy normal skin kept in cultures at an air-liquid interphase for 4 days...
January 21, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28100093/p19-targeted-abd-derived-protein-variants-inhibit-il-23-binding-and-exert-suppressive-control-over-il-23-stimulated-expansion-of-primary-human-il-17-t-cells
#18
Lucie Křížová, Milan Kuchař, Hana Petroková, Radim Osička, Marie Hlavničková, Ondřej Pelák, Jiří Černý, Tomáš Kalina, Petr Malý
Interleukin-23 (IL-23), a heterodimeric cytokine of covalently bound p19 and p40 proteins, has recently been closely associated with development of several chronic autoimmune diseases such as psoriasis, psoriatic arthritis or inflammatory bowel disease. Released by activated dendritic cells, IL-23 interacts with IL-23 receptor (IL-23R) on Th17 cells, thus promoting intracellular signaling, a pivotal step in Th17-driven pro-inflammatory axis. Here, we aimed to block the binding of IL-23 cytokine to its cell-surface receptor by novel inhibitory protein binders targeted to the p19 subunit of human IL-23...
January 19, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28096316/bay-11-7082-inhibits-the-nf-kb-and-nlrp3-inflammasome-pathways-and-protects-against-imq-induced-psoriasis
#19
Natasha Irrera, Mario Vaccaro, Alessandra Bitto, Giovanni Pallio, Gabriele Pizzino, Maria Lentini, Vincenzo Arcoraci, Letteria Minutoli, Michele Scuruchi, Giuseppina Cutroneo, Giuseppe Pio Anastasi, Roberta Ettari, Francesco Squadrito, Domenica Altavilla
BAY 11-7082 antagonizes I-κB kinase-β preventing nuclear translocation of NF-κB; it also inhibits NLRP3 inflammasome activation.NF-κB is involved in psoriasis, while the role of NLRP3 is controversial. We investigated BAY 11-7082 effects in an experimental model of psoriasis-like dermatitis. Psoriasis-like lesions were induced by a topical application of imiquimod cream (IMQ; 62.5 mg/day) on the shaved back skin of C57BL/6 and NLRP3 knock-out mice for 7 consecutive days. Sham psoriasis animals were challenged with vaseline cream...
January 17, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28026823/anti%C3%A2-cytokine-therapy-for-psoriasis-not-only-tnf%C3%A2-%C3%AE-blockers-overview-of-reports-on-the-effectiveness-of-therapy-with-il%C3%A2-12-il%C3%A2-23-and-t-and-b-lymphocyte-inhibitors
#20
Dominika Wcisło-Dziadecka, Martyna Zbiciak, Ligia Brzezińska-Wcisło, Urszula Mazurek
TNF‑α inhibitors - infliximab, etanercept and adalimumab - can be used in the treatment of psoriasis vulgaris and psoriatic arthritis, along with other inhibitors of proinflammatory cytokines, such as interleukin‑12 (IL‑12) and IL‑23. This paper presents the results of research on the use of biological drugs other than the tumor necrosis factor blockers (TNF‑α), namely inhibitors of IL‑12 and IL‑23 (ustekinumab), T‑cell inhibitors (alefacept and efalizumab), B‑cell inhibitors (rituximab), anti‑IL‑17 agents (secukinumab, ixekizumab, and brodalumab) and IL23p19 inhibitors (guselkumab and tildrakizumab)...
December 8, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
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