Pruritus in ordinary scabies: IL‐31 from macrophages induced by overexpression of thymic stromal lymphopoietin and periostin

Background Scabies is a common contagious skin disease caused by an infestation of the skin by Sarcoptes scabiei var. hominis. A hallmark symptom of scabies is severe itch. Methods We sought to determine the generation of a pruritogenic cytokine, interleukin (IL)‐31, together with immune profiles in skin lesions of ordinary scabies through immunohistochemical and immunofluorescent studies. To elucidate the pathological mechanisms of IL‐31 generation, murine peritoneal macrophages were stimulated with various T helper 2 (Th2) cytokines and proteins ex vivo. Results A large number of CCR4(+) Th2 cells, eosinophils, and basophils infiltrated in scabies lesions. Increased generation of IL‐31, thymic stromal lymphopoietin (TSLP), and periostin was also observed. A major population of IL‐31(+) cells were Arginase‐1(+)/CD163(+) M2 macrophages. Murine peritoneal macrophages showed an M2 phenotype and generated IL‐31 when stimulated with TSLP and periostin. Conclusion IL‐31 appeared to be largely generated by M2 macrophages in ordinary scabies lesions. This IL‐31 induction was mediated by TSLP and periostin. A large number of CCR4+ cells, basophils, and eosinophils were observed in human ordinary scabies lesions, suggesting that a Th2 immune response is predominant in ordinary scabies. Increased IL‐31, a pruritogenic cytokine, thymic stromal lymphopoietin (TSLP), and periostin were detected in the lesions. The majority of IL‐31+ cells were CD68+, Arg1+, and CD163+ M2 macrophages and IL‐31 could be induced by overexpression of TSLP and periostin. Arg1: arginase 1; CCR4: C‐C chemokine receptor type 4; TSLP: thymic stromal lymphopoietin