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The interleukin-17 pathway in psoriasis and psoriatic arthritis: disease pathogenesis and possibilities of treatment

The interleukin-17 pathway in psoriasis and psoriatic arthritis: disease pathogenesis and possibilities of treatment 1

The Interleukin-17 Pathway in Psoriasis and Psoriatic Arthritis: Disease Pathogenesis and Possibilities of Treatment. Psoriatic arthritis Psoriasis Interleukin-17 IL-17 Interleukin-23 IL-23 Biologic agents Pathogenesis Treatment. The Interleukin-17 Pathway in Psoriasis and Psoriatic Arthritis: Disease Pathogenesis and Possibilities of Treatment on ResearchGate, the professional network for scientists. The interleukin-17 pathway in psoriasis and psoriatic arthritis: disease pathogenesis and possibilities of treatment.

The interleukin-17 pathway in psoriasis and psoriatic arthritis: disease pathogenesis and possibilities of treatment 2Therapeutic agents targeting these cytokines and/or their receptors have now been developed as potential treatment strategies for common immune-mediated diseases. Anti-IL-17 and anti-IL-12/-23 regimens appear particularly effective in psoriasis, with promising results in spondyloarthropathies also emerging. Psoriatic arthritis (PsA) is a chronic inflammatory joint disorder with heterogeneous clinical features that may include plaque psoriasis, joint inflammation, enthesitis, dactylitis, and abnormal bone turn over. Pathophysiology of Plaque Psoriasis Provided the Initial Clues About the Biologic Mechanisms Underlying Psoriatic Arthritis. Editorial: emerging evidence for critical involvement of the interleukin-17 pathway in both psoriasis and psoriatic arthritis. IL17-targeted therapeutics are being developed to treat psoriasis. IL17 is involved in the pathogenesis of many diseases, and the implications of IL17 blockade. Deficiencies in the IL17 pathway can result in both bacterial and fungal infections and increased tumor growth. IL17 deficiency attenuates rheumatoid arthritis, atopic dermatitis, hapten-induced contact hypersensitivity and irritable bowel disease and is protective in lung cancer. Role of IL-17 in psoriasis and psoriatic arthritis.

Results from the FUTURE trials demonstrate significant reduction in disease burden and severity of PsA with secukinumab. The interleukin-17 pathway in psoriasis and psoriatic arthritis: disease pathogenesis and possibilities of treatment. The heterogeneous expression levels may explain nonresponse to anti-IL-17 therapy in subsets of patients. Interestingly, recent studies have demonstrated the plasticity of Th17 cells and have indicated their pathogenic role, especially when shifted towards Th1 cells 2 – 4. Interleukin 17A is a proinflammatory cytokine that is implicated in the pathogenesis of psoriatic arthritis. Subcutaneous secukinumab 300 mg and 150 mg improved the signs and symptoms of psoriatic arthritis, suggesting that secukinumab is a potential future treatment option for patients with this disorder. 17 to the pathogenesis of immune-mediated inflammatory diseases, such as psoriasis and psoriatic arthritis. ORodds ratio.

Therapeutic Targeting Of Il-17 And Il-23 Cytokines In Immune-mediated Diseases

Keywords: TH17, IL-17, IL-23, psoriasis, psoriatic arthritis, ankylosing spondylitis. IL-23 is the pivotal mediator responsible for TH17 differentiation and the IL-23/IL-17 axis has been strongly implicated in the pathogenesis of several immune mediated diseases, in particular chronic arthritis and skin psoriasis. The possibility that antagonism of this pathway may allow the key approach in the control of disease activity as well as disease damage in chronic arthritis and in other immune-mediated inflammatory diseases has been tested in vivo by means of several new biologic drugs, which target the IL-23/IL-17 axis, as summarized in Table 1. Ustekinumab has been assessed in two Phase III trials in psoriasis; in the first study, patients were treated with 45 mg, 90 mg, or placebo at baseline,37 after 4 weeks and then every 12 weeks. To evaluate the therapeutic efficacy and safety of anti-IL-17 agents in the treatment of psoriasis, we performed a systemic review and meta-analysis of the relevant published clinical trials, collectively referred to as secukinumab, ixekizumab and brodalumab. 5,6 evidence suggests that the TH17 cell cytokine IL-17 may play an important role in the pathogenesis of psoriasis 6. K. Interleukin-17A: a unique pathway in immune-mediated diseases: psoriasis, psoriatic arthritis and rheumatoid arthritis. Psoriasis is a long-lasting autoimmune disease characterized by patches of abnormal skin. These skin patches are typically red, itchy, and scaly. These treatments may include steroid creams, vitamin D3 cream, ultraviolet light, and immune system suppressing medications such as methotrexate. Psoriasis is associated with an increased risk of psoriatic arthritis, lymphomas, cardiovascular disease, Crohn’s disease, and depression. Psoriatic T cells move from the dermis into the epidermis and secrete interferon- and interleukin-17. Psoriatic keratinocytes produce several angiogenic cytokines, such as VEGF, interleukin-8 (IL-8), tumor necrosis factor- (TNF- ), and transforming growth factor- (TGF- ). Thus, the IL-23/IL-17 inflammatory pathway is central to the pathogenesis of psoriasis. View at Google Scholar View at Scopus; B. Beutler, Inferences, questions and possibilities in Toll-like receptor signalling, Nature, vol. Psoriatic arthritis is a chronic inflammatory arthritis that develops in at least 5 of patients with psoriasis. Arthroscopic synovectomy has been effective in treating severe, chronic, monoarticular synovitis. Thus, it appears that the interleukin-23Th17 axis is a predominant pathway to the induction of autoimmune disease.

Future Trials Lead To Novel Treatment For Psoriatic Arthritis

Based on the results of the Phase 2 and 3 clinical trials above, targeting the IL-17 pathway may be an additional effective and safe therapeutic option in the future for patients with psoriasis or psoriatic arthritis. Krueger JG, Bowcock A. Psoriasis pathophysiology: current concepts of pathogenesis. Secukinumab, a human anti-interleukin-17A monoclonal antibody, improves active psoriatic arthritis and inhibits radiographic progression: efficacy and safety data from a phase 3 randomized, multicenter, double-blind, placebo-controlled study. Soumya Reddy, MD, discusses the possibility of smoldering disease in patients whose inflammatory markers seem well-controlled.