Mechanisms in Acne Inversa Inflammatory Disease: Pathogenetic Deficiency of IL-22 Contributes to a Chronic

Overexpression of the T cell cytokine IL-22 is linked to the development of some chronic diseases, but little is known about IL-22 deficiency in humans. As demonstrated in this study, acne inversa (AI; also designated as Hidradenitis suppurativa) lesions show a relative deficiency of IL-22 and IL-20, but not of IL-17A, IL-26, IFN-g, IL-24, or IL-1b. Moreover, AI lesions had reduced expression of membranous IL-22 and IL-20 receptors and increased expression of the natural IL-22 inhibitor, IL-22 binding protein. AI is a chronic inflammatory skin disease with prevalence up to 4% of the population and in which cutaneous bacterial persistence represents an important pathogenetic factor. Accordingly, we also found a relative deficiency of antimicrobial proteins (AMPs) in AI lesions and a positive correlation between lesional IL-22 and IL-20 versus AMP levels. IL-22, like its tissue cell downstream mediator IL-20, upregulated AMPs in reconstituted human epidermis and was critical for increased AMP levels under inflammatory conditions. The relative IL-22 deficiency in AI was not linked to lesional T cell numbers or Th22/Th1/Th17 subset markers and-inducing cytokines. However, IL-10 was highly expressed in AI lesions and correlated negatively with IL-22 expression. Moreover, IL-10 inhibited IL-22 but not IL-17 production in vitro. The IL-10 overexpression, in turn, was not associated with an elevated presence of regulatory T cells but with the enhanced presence of an IL-10–inducing cytokine. We conclude that IL-22 deficiency may contribute to the pathogenesis of certain chronic disorders as postulated in this paper for AI. A cne inversa (AI; also referred to as Hidradenitis suppu-rativa) is a chronic inflammatory skin disease with a prevalence rate of up to 4% (1–6). It affects the inter-triginous skin of perianal, inguinal, and axillary sites (2, 5). Initially, the occlusion of apocrine or follicular ducts leads to stasis as well as to accumulation and propagation of bacteria in the apocrine hair follicle unit followed by dilatation and rupture of the unit, inflammation , and tissue destruction. The persistence of streptococci and staphylococci in obstructed and ruptured hair follicles maintains and boosts the inflammation and leads to a superfluous exu-date of purulence. Left untreated, AI results in the development of painful, fistulating sinuses and wide scars. The exact etiology of AI, however, is unknown. Smoking, obesity , a respective genetic background, and hormonal factors may play a role in its development and/or course (5). The assumption of cutaneous bacterial persistence in affected skin as a …