Increased β‐endorphin and autotaxin in patients with prurigo

Abstract

This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractObjectives: Prurigo is a treatment-resistant inflammatory disease of unknown etiology. Persistent and severe itch is a major and important clinical symptom, but pathological mechanisms and/or actual mediators for itch in prurigo remain to be defined. Methods:We investigated blood levels of β-endorphin, dynorphin A, and autotaxin in adult patients with prurigo (n = 18), including prurigo nodularis, prurigo chronica multiformis, and other forms. Patients with hemodialysis, hepatic dysfunction, and pregnancy were excluded. Immunofluorescence staining for β-endorphin and autotaxin in lesional skin was also performed. In addition, β-endorphin and autotaxin synthesis of cultured epidermal keratinocytes in response to several cytokine stimulation was assessed in vitro.Results: Blood levels of β-endorphin were higher in patients with prurigo than in control subjects (n = 20), while dynorphin A levels were comparable in the two groups.Blood autotaxin levels also were increased in patients with prurigo compared to control subjects. On the one hand, epidermal expression of β-endorphin was increased in skin lesions of prurigo chronica multiformis, but not in prurigo nodularis. On the other hand, enhanced expression of autotaxin was observed in the epidermis in both prurigo nodularis and prurigo chronica multiformis. In vitro studies showed that βendorphin-expressing epidermal keratinocytes increased following stimulation with TNF-α, interleukin-31, and/or IFN-γ. Autotaxin was also detected in the cytoplasm of cultured epidermal keratinocytes. The fraction of autotaxin-expressing cells increased when stimulated with TNF-α and/or interleukin-31.Conclusions: Imbalance of opioid receptor signals and/or the autotaxin-lysophosphatidic acid axis may contribute, at least in part, to the pathogenesis and intractable pruritus in some of the patients with prurigo.

Comprehensive plasma cytokine and chemokine profiling in prurigo nodularis reveals endotypes in Type 2 inflammation

“…In comparing cytokine levels of patients with PN to healthy controls, we found that IL-6, TNF-α, IL-12/IL23p40, MIP-1α/CCL3, MDC/CCL22, TSLP, IL-10, IL-15, sVCAM-1, sICAM-1, and SAA were significantly elevated. Prior studies have found elevated levels of CUB domain-containing protein 1 (CDCP1), Monocyte Chemotactic Protein 3 (MCP-3), IL-13, periostin, IL-31, IL-6, caspase 8, β-endorphin, and autotaxin in the blood of PN patients 5 – 7 , 23 – 25 . Several Th1/Th17 associated cytokines that were elevated in PN compared to HCs and have not been previously linked to PN include MIP-1α/CCL3 and IL-15.…”

Advances in Understanding the Initial Steps of Pruritoceptive Itch: How the Itch Hits the Switch

“…Endorphins are a group of OPRM agonists and are comprised of three endogenous opioid peptides, which are produced and stored in the pituitary gland [ 186 ]. It was shown that the plasma levels of β-endorphins are elevated in patients suffering from prurigo [ 187 ]. Thus, it can be hypothesized that imbalanced endorphin levels may contribute to pruritus.…”