Multiple itch-related and inflammation-related proteins

Multiple itch-related and inflammation-related proteins refers to a collective group of molecular mediators that bridge the immune and nervous systems to drive chronic pruritus and skin inflammation. This group primarily encompasses Type 2 cytokines—such as Interleukin-4 (IL-4), Interleukin-13 (IL-13), and Interleukin-31 (IL-31)—and their associated signaling enzymes, particularly Janus Kinase 1 (JAK1) (17.1.1, 17.1.5). These proteins are considered itch-related because they can directly bind to receptors on peripheral sensory neurons (pruriceptors) to trigger the sensation of itch, while their inflammation-related role involves promoting the recruitment of immune cells and the breakdown of the epidermal barrier (17.1.2, 17.1.5). Therapeutic targeting of this group is a cornerstone of modern dermatology, utilizing monoclonal antibodies like dupilumab (targeting IL-4Rα) and nemolizumab (targeting IL-31RA), or small-molecule JAK inhibitors like abrocitinib and upadacitinib, which block the signaling of multiple pruritogenic cytokines simultaneously (17.1.5). By addressing both the neural and immunological components of the disease, these therapies effectively interrupt the itch-scratch cycle in conditions such as atopic dermatitis and prurigo nodularis (17.1.1, 17.1.4).

Other names

Itch-related cytokinesInflammation-related cytokinesPruritogenic cytokinesType 2 cytokinesNeuroimmune itch mediatorsItchscriptome proteins

Inhibition of signaling pathways (primarily the JAK/STAT pathway) or direct neutralization of multiple cytokines (such as IL-4, IL-13, IL-31, and TSLP) that concurrently drive inflammatory cell infiltration and the activation of peripheral sensory neurons (pruriceptors).