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Il-23 and psoriasis

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28011143/dynamic-changes-in-resident-and-infiltrating-epidermal-dendritic-cells-in-active-and-resolved-psoriasis
#13
Elisa Martini, Maria Wiken, Stanley Cheuk, Irène Gallais Sérézal, Faezzah Baharom, Mona Ståhle, Anna Smed-Sörensen, Liv Eidsmo
Epidermal Langerhans cells (LCs) are spatially separated from dermal dendritic cells (DCs) in healthy human skin. In active psoriasis, maintained by local production of IL-23 and IL-17, DCs infiltrate both skin compartments. Here we show that CCR2(+) epidermal DCs (eDCs), phenotypically distinct from dermal DCs, were strictly confined to lesional psoriasis. The eDCs exceeded the number of LCs and displayed high expression of genes involved in neutrophil recruitment and the activation of keratinocytes and T cells...
December 20, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27999243/serum-levels-of-il-10-and-il-22-cytokines-in-patients-with-psoriasis
#14
Mohammad Reza Sobhan, Mahmood Farshchian, Ali Hoseinzadeh, Hamid Reza Ghasemibasir, Ghasem Solgi
BACKGROUND: As a chronic inflammatory condition, psoriasis results from an interaction between genetic and immunologic factors in a predisposing environment. In spite of compelling evidence for the role of T cells and cytokines in psoriasis, interleukin (IL)-10 and IL-22 have not been sufficiently investigated. OBJECTIVE: To assess the serum levels of IL-10 and IL-22 in patients with psoriasis compared to healthy controls. METHODS: A total of 28 patients with psoriasis were compared with 28 age and sex-matched healthy subjects...
December 2016: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/27984001/psoriatic-inflammation-enhances-allergic-airway-inflammation-through-il-23-stat3-signaling-in-a-murine-model
#15
Ahmed Nadeem, Naif O Al-Harbi, Mushtaq A Ansari, Mohammed M Al-Harbi, Ahmed M El-Sherbeeny, Khairy M A Zoheir, Sabry M Attia, Mohamed M Hafez, Othman A Al-Shabanah, Sheikh F Ahmad
Psoriasis is an autoimmune inflammatory skin disease characterized by activated IL-23/STAT3/Th17 axis. Recently psoriatic inflammation has been shown to be associated with asthma. However, no study has previously explored how psoriatic inflammation affects airway inflammation. Therefore, this study investigated the effect of imiquimod (IMQ)-induced psoriatic inflammation on cockroach extract (CE)-induced airway inflammation in murine models. Mice were subjected to topical and intranasal administration of IMQ and CE to develop psoriatic and airway inflammation respectively...
January 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27982014/monocyte-derived-inflammatory-langerhans-cells-and-dermal-dendritic-cells-mediate-psoriasis-like-inflammation
#16
Tej Pratap Singh, Howard H Zhang, Izabela Borek, Peter Wolf, Michael N Hedrick, Satya P Singh, Brian L Kelsall, Bjorn E Clausen, Joshua M Farber
Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined. Here we show that DCs are required for psoriasis-like changes in mouse skin induced by the local injection of IL-23. However, Flt3L-dependent DCs and resident Langerhans cells are dispensable for the inflammation. In epidermis and dermis, the critical DCs are TNF-producing and IL-1β-producing monocyte-derived DCs, including a population of inflammatory Langerhans cells. Depleting Ly6C(hi) blood monocytes reduces DC accumulation and the skin changes induced either by injecting IL-23 or by application of the TLR7 agonist imiquimod...
December 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27964879/activation-of-langerhans-cells-promotes-the-inflammation-in-imiquimod-induced-psoriasis-like-dermatitis
#17
Chunying Xiao, Zhenlai Zhu, Shuhong Sun, Jixin Gao, Meng Fu, Yufeng Liu, Gang Wang, Xu Yao, Wei Li
BACKGROUND: Langerhans cells (LCs) are epidermis-resident dendritic cells that sense and mediate stimuli from skin and outside world, and participate in various skin diseases, playing either pro-inflammatory or regulatory roles. However, the exact function of LCs in the pathogenesis of psoriasis remains unclear, and the conclusions of previous studies are controversial. OBJECTIVES: To explore the role of LCs in mouse model of imiquimod (IMQ)-induced psoriasis-like dermatitis using langerin-diphtheria toxin A (DTA) mice that are constitutively deficient in LCs...
December 5, 2016: Journal of Dermatological Science
https://www.readbyqxmd.com/read/27964744/differential-gene-and-protein-expression-of-chemokines-and-cytokines-in-synovial-fluid-of-patients-with-arthritis
#18
Anastasiya Muntyanu, Fatima Abji, Kun Liang, Remy A Pollock, Vinod Chandran, Dafna D Gladman
BACKGROUND: Psoriatic arthritis (PsA), an inflammatory musculoskeletal disease, develops in approximately 30% of patients with psoriasis. Previously, chemokine (C-X-C motif) ligand 10 (CXCL10) was identified as a predictive biomarker of PsA in patients with psoriasis and was reduced after development of PsA. The purpose of the present study was to explore messenger RNA (mRNA) and protein expression of CXCL10 and its receptor, chemokine (C-X-C motif) receptor 3 (CXCR3), in the joints of patients with PsA to gain insight into their role in the pathogenesis of the disease...
December 13, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27956825/ustekinumab-in-treatment-of-crohn-s-disease-design-development-and-potential-place-in-therapy
#19
REVIEW
Parakkal Deepak, Edward V Loftus
Crohn's disease is characterized by a dysregulation of both innate and adaptive immunity responses. Interleukin-12/23 (IL-12/23) pathway has been found to be a major driver of inflammation in adaptive immune responses. Ustekinumab is a fully human immunoglobulin G1 kappa monoclonal antibody that blocks the p40 subunit of IL-12 and IL-23 and prevents their interaction with their cell surface receptor and further cytokine activation. It is currently approved in the management of plaque psoriasis and psoriatic arthritis...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27942589/interleukin-6-regulates-psoriasiform-inflammation-associated-thrombosis
#20
Yunmei Wang, Jackelyn B Golden, Yi Fritz, Xiufen Zhang, Doina Diaconu, Maya I Camhi, Huiyun Gao, Sean M Dawes, Xianying Xing, Santhi K Ganesh, Johann E Gudjonsson, Daniel I Simon, Thomas S McCormick, Nicole L Ward
Psoriasis patients are at increased risk of heart attack and stroke and have elevated MRP8/14 levels that predict heart attack. The KC-Tie2 psoriasiform mouse model exhibits elevated MRP8/14 and is prothrombotic. Mrp14(-/-) mice, in contrast, are protected from thrombosis, but, surprisingly, KC-Tie2xMrp14(-/-) mice remain prothrombotic. Treating KC-Tie2xMrp14(-/-) mice with anti-IL-23p19 antibodies reversed the skin inflammation, improved thrombosis, and decreased IL-6. In comparison, IL-6 deletion from KC-Tie2 animals improved thrombosis despite sustained skin inflammation, suggesting that thrombosis improvements following IL-23 inhibition occur secondary to IL-6 decreases...
December 8, 2016: JCI Insight
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