Glucocorticoids and Glucocorticoid-Induced-Leucine-Zipper (GILZ) in Psoriasis
Psoriasis is a prevalent chronic inflammatory human disease initiated by impaired function of immune cells and epidermal keratinocytes, resulting in increased cytokine production and hyperproliferation, leading to skin lesions. Overproduction of Th1- and Th17-cytokines including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-23, IL-17, and IL-22, is a major driver of the disease. Glucocorticoids (GCs) represent the mainstay protocol for treating psoriasis as they modulate epidermal differentiation and are potent anti-inflammatory compounds. The development of safer GC-based therapies is a high priority due to potentially severe adverse effects associated with prolonged GC use. Specific efforts have focused on downstream anti-inflammatory effectors of GC-signaling such as GC-Induced-Leucine-Zipper (GILZ), which suppresses Th17 responses and antagonizes multiple pro-inflammatory signaling pathways involved in psoriasis, including AP-1, NF-κB, STAT3, and ROR-γt. Here we review evidence regarding defective GC signaling, GC receptor (GR) function, and GILZ in psoriasis. We discuss seemingly contradicting data on the loss- and gain-of-function of GILZ in the imiquimod-induced mouse model of psoriasis. We also present potential therapeutic strategies aimed to restore GC-related pathways.
Publication date: Available online 19 October 2019Source: Autoimmunity ReviewsAuthor(s): Andrea Rubbert-Roth, Melinda Zsuzsanna Szabó, Melinda Kedves, György Nagy, Fabiola Atzeni, Piercarlo Sarzi-PuttiniAbstractThe five TNF inhibitors currently approved for the treatment of RA are characterised by differences in their molecular structures, half-lives, administration routes, dosing intervals, immunogenicity, and use in women who wish to become pregnant. TNF inhibitors still represent the first biologic after conventional synthetic DMARD (csDMARD) in the majority of patients according to registry data. This was p...
PMID: 31627796 [PubMed - in process]
Abstract Crosstalk between the immune system and the nervous system, via neurotransmitters such as dopamine, is increasingly of interest as we begin to learn how lymphocytes in peripheral tissues can both produce and respond to these molecules. This crosstalk can modulate immune responses by influencing the local tissue environment and can, for instance, influence the activation status and migration of T cells. Immune cells also use neurotransmitters to communicate with each other. Understanding how neurotransmitters influence the immune system may provide novel approaches for targeting diseases associated with ti...
Authors: Makrantonaki E PMID: 31620817 [PubMed - as supplied by publisher]
ConclusionsOverall, in this study with more than 70% of patients with moderate disease, patients reported high burden of disease and impact on QoL. This study demonstrates the importance of considering patient perspectives in treatment decisions that are critical for optimizing patient outcomes.FundingEli Lilly and Company.
A study in mouse models with psoriasis-like skin inflammation suggests that ketogenic diets with a very high fat content may exacerbate skin problems.
Secukinumab for patients failing previous TNFα-inhibitor therapy: results of a randomised open-label study (Signature). Br J Dermatol. 2019 Oct 18;: Authors: Warren RB, Barker J, Finlay AY, Burden AD, Kirby B, Armendariz Y, Williams R, Hatchard C, Khare S, Griffiths CEM Abstract BACKGROUND: Efficacy data on therapies for psoriasis patients who have failed tumour necrosis factor (TNF)α-inhibitor therapy is limited. OBJECTIVES: To determine the effectiveness and tolerability of secukinumab, an IL-17A inhibitor, in patients with moderate/severe chronic plaque psoriasis with documented ef...
PUVA phototherapy is the therapeutic use of psoralens and UVA light to treat inflammatory skin diseases, with psoriasis the prototype disease. Naturally occurring phototoxic compounds, psoralens interact with UVA to suppress DNA synthesis and cell proliferation and induce apoptosis of inflammatory cells. Well-developed therapeutic protocols for psoriasis guide psoralen and UVA doses, treatment frequency, and safety measures, and these protocols also may be used to treat other inflammatory dermatoses.
This article covers fundamental considerations for physicians using NBUVB and highlights changes in the newest guideline recommendations for phototherapy treatment. Protocols for treatment initiation, maintenance, dose increases, and maintenance are compared and discussed. Readers will achieve a greater understanding of the fundamentals of NBUVB phototherapy and promising advances in the field, including home phototherapy and combination treatment.
Conclusions: It appears that further studies are necessary to explain this problem, perhaps to include an evaluation of TF levels in psoriatic skin. PMID: 31616219 [PubMed]