IL-31 drives **atopic dermatitis** and **prurigo nodularis** itch; Nemolizumab targeting IL-31RA demonstrates efficacy.

Atopic dermatitis (AD) and prurigo nodularis (PN) are chronic inflammatory skin conditions characterized by intense itch and debilitating skin lesions. Current treatments often fall short for many patients, highlighting a critical need for targeted therapies that address underlying mechanisms. Interleukin-31 (IL-31) has emerged as a central player in these conditions, driving both the debilitating pruritus and the underlying inflammatory and structural skin changes. Understanding its precise neuroimmune mechanisms is crucial for developing effective interventions.

This narrative review integrated the mechanistic biology of Interleukin-31 (IL-31) across both atopic dermatitis and prurigo nodularis with the comprehensive clinical evidence base for nemolizumab, a humanized monoclonal antibody specifically targeting IL-31RA. The authors meticulously examined various data sources, including findings from phase 3 clinical trials, long-term extension study results, translational biomarker evidence, and emerging real-world experience to synthesize current understanding of IL-31's role and nemolizumab's therapeutic efficacy.

The review established Interleukin-31 (IL-31) as the principal pruritogenic cytokine in both conditions, driving intense itch through direct neuronal activation via the IL-31RA/OSMRβ signaling axis. Beyond its direct neuroimmune effects, IL-31 also functions as a key immunological amplifier, sustaining Th2 polarization by promoting continued IL-4 and IL-13 production, thereby exacerbating the chronic inflammatory cascade. > IL-31 directly disrupts epidermal barrier integrity and acts on dermal fibroblasts to drive collagen synthesis and extracellular matrix remodeling, contributing to the characteristic lichenification in chronic atopic dermatitis and hyperkeratotic nodule formation in prurigo nodularis. Clinical evidence for nemolizumab, an IL-31RA antibody, from phase 3 trials, long-term extensions, and real-world data consistently demonstrated its efficacy in significantly reducing itch and improving skin lesions in both atopic dermatitis and prurigo nodularis patients. The review highlighted nemolizumab's ability to effectively interrupt the IL-31-mediated itch-scratch cycle and mitigate downstream inflammatory and structural skin changes.