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Transient Receptor Potential Channels and Itch
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Mahar Fatima, Jingyi Liu, Bo Duan
Alteration in cytokine profiles can result in pruritus. Notably, excessive levels of Interleukin-31 (IL-31), a cytokine produced by TH2 cells, can result in atopic-like dermatitis (46). IL-13 induces calcium influx in TRPV1+ DRG neurons. Administration of IL-31 either cutaneously or intrathecally induces dose-dependent scratching bouts. IL-31 receptor A is expressed by a subset of the TRPV1+ population. Pharmacological ablation of TRPV1+ sensory nerves also culminates in the loss of IL31 receptor A-positive nerve terminals in the dorsal spinal cord. IL-13 induced scratching responses are dramatically reduced in TRPV1+ neuron-ablated or Trpv1 KO mice (47).
Pruritus in Atopic Dermatitis: Pathophysiology and Treatment Options
Published in Donald Rudikoff, Steven R. Cohen, Noah Scheinfeld, Atopic Dermatitis and Eczematous Disorders, 2014
Tejesh Surendra Patel, Gil Yosipovitch
A unique feature of itch is that it is restricted to the skin, mucous membranes, and cornea – no other tissue experiences pruritus (Charlesworth and Beltrani 2002). Current evidence suggests that the itch sensation emanates from activity in nerve fibers located in the epidermis. Although a specific epidermal itch receptor has not yet been clearly identified, it has been shown that removal of the epidermis abolishes the perception of pruritus (Shelley and Arthur 1957). Recent studies suggest that there are indeed itch-specific receptors in the skin. Certain C-nerve fibers containing Mas-related, G-protein-coupled receptor member A (MRGPRA), a subfamily of G-protein-coupled receptors, have been shown to mediate chloroquine-induced itch (Liu et al. 2009). A mutation in the oncostatin M receptor (OSMR) gene has recently been identified in patients with lichen amyloidosis, a localized pruritic condition most common in Hispanic and Asian individuals (Tanaka et al. 2009). This gene encodes OSMR-b, an interleukin-31 (IL-31) cytokine receptor. IL-31 is thought to elicit itch in atopic dermatitis and prurigo nodularis patients. Interestingly, keratinocytes express an array of neural mediators and receptors, all of which appear to be involved with the sensation of itch (Denda 2002). These neural mediators include opioids, proteases, substance P, nerve growth factor, neurotrophin-4, and endocannabinoids. Keratinocytes also express voltage-gated ATP channels and adenosine receptor ligands – similar to C-nerve fibers involved in transmission of the perception of pain (Inoue et al. 2002). It is thus possible that keratinocytes are involved in generating and transducing the itch sensation through these channels in a manner similar to pain.
Therapeutic potential of biologics in prurigo nodularis
Published in Expert Opinion on Biological Therapy, 2022
Svenja Müller, Thomas Bieber, Sonja Ständer
IL-31 is produced and released in the largest quantity by CD4+ helper type 2 (Th2) cells after interleukin-4 induced gene expression [38,42]. Other IL-31 releasing cells include skin-homing CD45RO+ (memory) T cells, dendritic cells, mast cells, CD68+ macrophages, basophils, and eosinophils [32,38,41]. IL-4/STAT 6 and IL-33/NF-κB pathways mediate the induction of IL-31 protein [43]. Interleukin-31 binds to a heterodimeric receptor complex consisting of IL-31 receptor α (IL-31RA) and oncostatin M receptor β (OSMRβ) which is present at epithelial cells including keratinocytes, monocytes/macrophages, mast cells, dendritic cells, basophils and cutaneous (IL-31RA/TRPV1+/TRPA1+) C fibers and in highest density in dorsal-root ganglia neurons [13,28,38,40,44]. These IL-31-affine dorsal-root ganglia neurons possess sensors for both pruritogens and neurogenic inflammation mediators [13]. Moreover, IL-31 activates the janus kinases JAK1 and JAK2, which are important for pruritus signaling as well, by the induction of phosphorylation [13].
Implication of Increased Serum IL-31 for Primary Biliary Cholangitis
Published in Immunological Investigations, 2021
Ning Mu, Feng Lin, Zhiguo Jiang, Yan Liang, Zaixing Yang
Interleukin-31 (IL-31), belonging to the gp130/IL-6 cytokine family, is expressed and secreted by some immune and other cells, especially, CD4 + T helper cells and mast cells (Di Salvo et al. 2018; Ferretti et al. 2017). This cytokine has diverse biological functions, including inducing proinflammatory cytokines, regulating cell proliferation, mediating immune and inflammatory damage (Di Salvo et al. 2018). It has been found that the transcripts and protein levels of IL-31 are increased in some skin diseases, such as atopic dermatitis (Kim et al. 2011), atopic contact dermatitis (Neis et al. 2006) and Bullous pemphigoid (Rüdrich et al. 2018). Furthermore, IL-31 may be involved in pruritus of these skin diseases (Bağci and Ruzicka 2018; Furue et al. 2018; Gibbs et al. 2019). Additionally, increased IL-31 has also been seen in other autoimmune diseases including systemic lupus erythematosus (Huang et al. 2016) and axial spondyloarthritis (Rosine et al. 2018). Nowadays, there has been no study reporting the association between IL-31 and PBC.
Therapy for pruritus in the elderly: a review of treatment developments
Published in Expert Opinion on Pharmacotherapy, 2018
Manuel P. Pereira, Sonja Ständer
Interleukin-31 plays an important role in the pathway of pruritic atopic dermatitis, being elevated in the serum of these patients [57]. Nemolizumab, a monoclonal antibody blocking the interleukin-31 receptor A, is a promising future drug for atopic dermatitis. In a phase II clinical trial with 216 patients lasting for 12 weeks, nemolizumab administered subcutaneously at different doses (0.1, 0.5, and 2.0 mg/kg body weight) once every 4 weeks substantially reduced the pruritus intensity in patients with moderate and severe atopic dermatitis. A study over a longer period of time that includes a larger number of patients is needed to better understand the possible side effects associated with this medication [58]. This trial followed another smaller study evaluating the safety of this drug in healthy volunteers and patients with atopic dermatitis. No serious adverse events were recorded [59]. Clinical trials testing nemolizumab in patients with chronic prurigo are soon to begin (NCT03181503).