Experimentallu Induced Psoriatic Lesions Associate with Rapid but Transient Decrease in Interleukin-33 Immunostaining in Epidermis

Abstract

A slight epidermal damage can induce the Köbner reaction in psoriasis, and the “alarmin”, interleukin-33 (IL-33), may be involved in this process. Therefore, the uninvolved psoriatic skin was tape-stripped, and skin biopsies were collected at 0 day, 2 h and 3 days or at 0 day, 1 day and 7 days for immunohistochemistry. Eight patients out of 18 with the positive Köbner reaction showed a decrease in epidermal thickness and revealed transient reduction in epidermal nuclear immunostaining of IL-33 in 2-h, 1-day, 3-day biopsies compared to the 10 Köbner-negative patients. In keratinocyte cultures, the full-length 32-kDa IL-33 was detected after damaging the cells with freeze-thawing. Interestingly, a very low concentration of rh-IL-33 (0.001–0.01 ng/ml) significantly stimulated (3)H-thymidine uptake by human LAD2 mast cells, but not by psoriatic peripheral blood mononuclear cells. The results show that epidermal IL-33 associates with positive Köbner response, and only a small amount of the IL-33 apparently released may induce proliferation in dermal mast cells.

Levocetirizine for the treatment of itch in psoriasis patients: An open‐label pilot study in a real‐world setting

“…Finally, MCs not only appear to play a special role in the early phase but also in the perpetuation of psoriatic inflammation [Schubert & Christophers, 1985;Suttle et al, 2015;Toruniowa & Jablonska, 1988). H1 stimulation has been shown to enhance the expression of TNFα, IL-6, IL-8, and intracellular adhesion molecules (ICAM-1) in keratinocytes (Harvima et al, 2008;Matsubara, Tamura, Ohmori, & Hasegawa, 2005).…”

“…In a recently published trial, clemastine and levocetirizine reduced itch by approximately 40% (Domagala, Szepietowski, & Reich, 2017), and previous studies showed that psoriasis patients used antihistamines with variable benefit (Amatya et al, 2008;Chang, Han, Jung, & Choi, 2007;Moriue et al, 2013;Prignano et al, 2009;Yosipovitch et al, 2020). Moreover, mast cells (MC) appear to be implicated in the early phase as well as in perpetuation of psoriasis inflammation (Schubert & Christophers, 1985;Suttle et al, 2015;Toruniowa & Jablonska, 1988). Additionally, there is evidence of a direct MC-nerve interaction (Naukkarinen et al, 1996;Naukkarinen, Harvima, Paukkonen, Aalto, & Horsmanheimo, 1993) with complex mutual regulations including stress-induced histamine release (Harvima, Nilsson, Suttle, & Naukkarinen, 2008), possibly contributing to itch (Chen & Lyga, 2014).…”

Pathogenic Role of Cytokines and Effect of Their Inhibition in Psoriasis

“…Relatively few studies have demonstrated the pathogenic association between IL-33 and psoriasis. Suttle et al [100] reported decreased IL-33 immunostaining in biopsies in Koebner-positive psoriasis patients, which can reflect the release of IL-33 after skin injury by tape stripping. Interestingly, the proinflammatory cytokine TNF-α dose-and time-dependently activated IL-33 mRNA expression in normal skin cultures ex vivo.…”

Methotrexate, but not narrowband ultraviolet B radiation, suppresses interleukin‐33 mRNA levels in psoriatic plaques and protein levels in serum of patients with psoriasis

“…IL‐33 levels are significantly increased in affected skin in patients with psoriasis, as compared with those in healthy skin and in patients with other inflammatory skin disorders . Suttle et al . have suggested that IL‐33 is released from epidermal keratinocytes after slightly damaging the skin surface in psoriasis.…”

“…4,5 IL-33 levels are significantly increased in affected skin in patients with psoriasis, as compared with those in healthy skin and in patients with other inflammatory skin disorders. [4][5][6] Suttle et al 7 have suggested that IL-33 is released from epidermal keratinocytes after slightly damaging the skin surface in psoriasis. Additionally, recent studies have demonstrated that serum IL-33 levels are increased in patients with psoriasis, indicating that IL-33 may represent a novel marker of the disease.…”