Recent understanding of disease susceptibility, severity markers, and mechanisms have helped to develop targeted therapy for itch in AD, including monoclonal antibodies against IL-4, IL-13, thymic stromal lymphopoietin (TSLP), IgE and IL-31.
These results suggest that the IL-31 axis and IL-31RA axis play as critical a role in the induction of scratching in primates as in mice and that the blockade of IL-31 signalling by an anti-human IL-31RA antibody is a promising therapeutic approach for treatment of AD.
A link between IL-31 and atopic dermatitis was shown by studying the phenotype of IL-31 transgenic mice and IL-31 gene haplotypes in patients suffering from dermatitis.
IL-31 expression correlates with the expression of IL-4 and IL-13 and is associated with atopic dermatitis in humans, indicating that IL-31 is involved in Th2-mediated skin inflammation.
It was initially identified as being associated with the promotion of atopic dermatitis, where increased levels of IL-31 levels have been found and IL-31 induced the expression of proinflammatory cytokines and chemokines in a human bronchial epithelial cell line.
IL-31R expression and regulation as well as functional effects of IL-31 stimulation were then investigated at both the mRNA and protein level and compared with HPKs from patients with AD.
This study presents the first genetic risk factor for the nonatopic type of eczema and indicates a primary role of IL-31-induced pruritus in the initiation of this disease, thus proposing a new target for the prevention and therapy of eczema.
Furthermore, H1R antagonist reduced the level of IL-31, a cytokine involving the skin barrier and pruritus, in chronic dermatitis lesions in NC/Nga mice and patients with AD.
In addition, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) results demonstrated that the mRNA expression of tumor necrosis factor (TNF)‑α, interferon (IFN)‑γ, interleukin (IL)‑4, IL‑13, IL‑31 and IL‑17A was reduced in ear skin following AXE administration in AD mice.
Therefore, IL-31 has been thought to be an important cytokine for regulating pruritus and AD disease activity; however, how IL-31 is involved in the immune response in AD has remained largely unknown.
Ca<sup>2+</sup> imaging, immunohistochemistry, quantitative real-time PCR, RNA sequencing, knockdown, cytokine/phosphokinase arrays, enzyme immune assay, and pharmacologic inhibition were performed to examine the cellular basis of the IL-31-stimulated, BNP-related itch signaling in dorsal root ganglionic neurons (DRGs) and skin cells, transgenic AD-like mouse models, and human skin of patients with AD and healthy subjects.
IL-31 is thought to play a role transmitting itch sensation to the central nervous system, and blocking IL-31 activity reduces itch in patients with AD.
These results demonstrate that an IL-31 mAb can inhibit IL-31-mediated pruritus in vivo, and could be an effective therapy for pruritic skin conditions like AD where IL-31 upregulation may play a role.
Interleukin-31 (IL-31) is a recently identified cytokine produced by Th2 cells that is involved in the development of atopic dermatitis-induced skin inflammation and pruritus.
ASC-exosomes also significantly reduced mRNA expression of various inflammatory cytokines such as interleukin (IL)-4, IL-23, IL-31, and tumor necrosis factor-α (TNF-α) in AD skin lesions of Nc/Nga mice.
Overexpression of interleukin-31, independent of mast cells and lymphocytes, induces clinical and histological features consistent with atopic dermatitis.