Upregulation of IL-36 cytokines in folliculitis and eosinophilic pustular folliculitis

Background: Members of the interleukin (IL)-36 family, IL-36α, IL-36β and IL-36γ, are potent chemoattractive cytokines for neutrophils and eosinophils. IL-36 receptor antagonist (IL-36Ra) inhibits IL-36α, IL-36β and IL-36γ activity. However, the immunohistological expression of IL-36α, IL-36β, IL-36γ and IL-36Ra has never been addressed in normal follicles, folliculitis or eosinophilic pustular folliculitis (EPF). Methods: We performed immunohistochemical staining for IL-36α, IL-36β, IL-36γ and IL-36Ra using 10 cases of EPF, nine of non-specific folliculitis, 10 normal skin samples and 10 samples of normal follicles adjacent to a sebaceous naevus as a control. Two dermatologists, who were blind to the patient records, evaluated all of the slides. Results: The immunoreactive IL-36α was hardly detected in the follicular epithelium and epidermis in the normal skin, folliculitis or EPF. The expression of IL-36β, IL-36γ and IL-36Ra was augmented in both folliculitis and EPF compared with that in normal follicles. Negative correlations were detected between IL-36β and IL-36Ra and between IL-36γ and IL-36Ra in normal follicles; however, these were absent in folliculitis. In contrast to normal follicles and folliculitis, a significant positive correlation between IL-36β/γ and IL-36Ra was shown in EPF. Conclusions: The overexpression of IL-36β, IL-36γ and IL-36Ra is an integral part of the inflammatory response of folliculitis and EPF. The coordinated expression of IL-36γ and IL-36Ra may be related to the pathomechanism of EPF.