Increased levels of lipocalin 2 in palmoplantar pustular psoriasis

•PPP is a recalcitrant chronic skin disease, whose pathogenic players are unexplored.•LCN2 blood levels are increased in PPP, correlate with pustule formation and indicate patients’ epidermal IL-1β activity and pro-atherogenic risk.•IL-1β inhibition may be a promising therapeitic approach in PPP, in particular in patients with high LCN2 levels. Palmoplantar pustular psoriasis (PPP) is a recalcitrant chronic skin disease affecting the palms and soles. To identify and characterize pathogenetic players in PPP. Clinical and anamnestic data as well as skin and blood samples of 60 PPP patients were collected. Healthy participants served as controls. Analysis of patient samples and cultured primary skin cells was performed by ELISA, qRT-PCR, and immunohistochemistry. Upon screening of blood mediators in PPP patients, lipocalin 2 (LCN2) emerged as being significantly upregulated compared to healthy participants. LCN2 blood levels were independent of age, sex, or concomitant psoriasis vulgaris. Keratinocytes in PPP skin lesions were important LCN2 producers. In vitro, LCN2 production of these cells was upregulated by IL-1β and further enhanced by IL-17 and TNF-α, while IL-22 had no effect. Accordingly, a positive relationship between blood IL-1β and LCN2 levels was evident in PPP. LCN2 blood levels also showed a positive correlation with PPP pustule score, Dermatology Quality of Life Index and blood levels of the pro-atherogenic molecule resistin. In PPP, increased blood levels of LCN2 indicate an important activity of IL-1β in the epidermis, may contribute to skin neutrophil infiltration, and may point to an increased pro- atherosclerosis risk.