Increased serum levels of IL‐22 in patients with nickel contact dermatitis

Abstract

Nickel can elicit both Th1-type andTh2-type responses in vitro (1) inpatients with nickel allergic contactdermatitis,butthiscomplexcytokinecascade has still to be clarified. Therecently discovered Th17 subset,which has crucial functions in hostdefence against infections and hasbeen implicated in the developmentofautoimmunediseases(2),hasbeensupposed to play an important rolein some inflammatory and autoim-mune skin disorders, such as contacthypersensitivity(3)andpsoriasis(4),respectively. Th17 cells are charac-terized by expression of interleukin(IL)-6, tumour necrosis factor-a,granulocyte–macrophage colony-stimulating factor, IL-17A, IL-17F,IL-21, IL-22, and IL-26 (5).Among these cytokines, IL-22,a member of the IL-10 cytokine fam-ily, described as having proinflam-matory activities on liver, pancreas,intestine, and skin (reviewed in 6),has been demonstrated to have a cru-cial function in the development ofdermal inflammation and epidermalacanthosis induced by IL-23 in mice(4). Moreover, IL-22 seems to beinvolved in the pathogenesis of psori-asis in humans, as demonstrated bythehighserumlevelsshowedbypsori-atic patients and the high levels pro-duced by T cells isolated by psoriaticskin (6), where the IL-22 receptor isexpressed on a variety of epithelialtissues(4).However,nodataareavail-ableon thepossibleroleplayed byIL-22in nickel contacthypersensitivityinhumans, thus we measured the circu-latinglevelsofthiscytokineinpatientswith allergic nickel contact dermatitis.We enrolled 31 female patientsaffected by allergic contact dermatitisto nickel (mean age 31.9 years; range17–64 years) diagnosed followingpatch testing in accordance withthe International Contact DermatitisResearch Group guidelines. Bloodsamples were collected after patchtesting during a period of clinicalremission 1 month after nickel con-tact avoidance.15 sex- and age-matched blooddonors, with no contact dermatitisand negative patch tests, were re-cruited as controls. Each subject gavepreviously used written, informedconsent to the study.Serum IL-22 was measured usingan enzyme-linked immunosorbentassay kit (R&D System Europe,Abingdon, UK). All samples wereanalysed in duplicate.Differences in IL-22 blood levelswere assessed by the Student’s t-testfor unpaired comparison, assumingunequal variances. Data were ex-pressed as mean standard devia-tion. A P value <0.05 was consideredto be significant.IL-22 serum levels were signifi-cantly higher in patients affected bycontact dermatitis compared withcontrols (17.10 9.50 pg/ml versus8.61 7.25 pg/ml, P ¼ 0.002)(Fig. 1). No correlation between IL-22 levels and age was found.About 10 years ago, it was demon-stratedthatnickel-specificCD4Tcellsexpressing the cutaneous lymphocyte-associated antigen skin-homingrecep-tor can synthesize and release IL-17and that IL-17 modulates variousproinflammatory functions of kerati-nocytes, especially when actingtogether with interferon-g and IL-4(7). Zheng et al. have recently demon-strated that the injection of IL-23(a Th17-inducing cytokine) into miceears induces a model of psoriasis-likelesions characterized by epidermalacanthosis with inflammatory cellularinfiltration mediated by IL-17 andIL-22. These features decrease inIL-22-deficient mice (4), and theadministration of IL-22 neutralizingautoantibodies reduces acanthosis,inflammatory infiltrates, and expres-sion of Th17 cytokines (8). However,thehistologicalfeaturesfoundinthesemurine models are not exclusivelycharacteristic of psoriasis but of aller-gic contact dermatitis as well.*Theseauthorscontributedequallytothis work.