Single cell analysis of clinically resolved epidermal skin from nickel-challenged individuals treated with either anakinra or placebo

Background: Topical corticosteroids are used as a standard treatment option in allergic contact dermatitis (ACD). However, the treatment doesn’t inhibit the generation of skin-resident memory T (TRM) cells. These cells play an important role in the pathogenesis of skin flare ups in ACD. Currently, findings in murine models suggest interleukin (IL)-1 inhibition can suppress the immune response to contact allergens. Objectives: To determine if IL-1 inhibition can attenuate acute skin flare-ups and restrict the development of TRM cells. Methods: A murine model was used to investigate the role of IL-1 on epidermal TRM cells by measuring changes in ear thickness and T cell composition. Next, we conducted a randomized, double-blinded, placebo-controlled trial (RCT) [H-22001652; EudraCT number: 2021-004750-39]. Nickel allergic participants were patch-tested at 1) baseline, 2) while being treated with either anakinra or placebo, 3) and 21 days after treatment. The primary outcome was the International Contact Dermatitis Research Group (ICDRG) score 48 hours after patch test application. While secondary outcomes were a reduction of immune cells in clinically cleared and actively inflamed skin. Results: In mice, IL-1 inhibition decreased the number of epidermal CD8+ TRM cells and attenuated skin flare-ups upon re-exposure. Twenty participants were enrolled and completed the RCT, but anakinra failed to improve ICDRG scores. Conclusions: Although IL-1 inhibition has been proven successful in murine models for ACD, there is currently no clinical evidence that suggest it being efficacious as a short-term treatment option for acute skin flare-ups in humans.