IL‐18 is involved in the pathogenesis of atopic dermatitis, psoriasis, and allergic contact dermatitis. CXCL9, CXCL10, and CXCL11 recruit type 1 T cells, and the production of these chemokines by keratinocytes is enhanced in these dermatoses. We examined the in vitro effects of IL‐18 on IFN‐γ‐induced CXCL9, CXCL10, and CXCL11 production in human keratinocytes. IL‐18 enhanced the IFN‐γ‐induced secretion and mRNA expression of CXCL9, CXCL10, and CXCL11 in parallel to the activation of NF‐κB, STAT1, and IFN‐regulatory factor (IRF)‐1. Antisense oligonucleotides against NF‐κB p50, p65, or STAT1 suppressed CXCL9, CXCL10, and CXCL11 production, and antisense IRF‐1 suppressed CXCL11 production. Inhibitors of PI3 K, p38 MAPK, and MEK suppressed IL‐18 plus IFN‐γ‐induced CXCL9, CXCL10, and CXCL11 production and NF‐κB, STAT1, and IRF‐1 activities. IL‐18 induced phosphorylation of ERK and Akt, while IFN‐γ induced phosphorylation of p38 MAPK. These results suggest that IL‐18 may potentiate IFN‐γ‐induced CXCL9, CXCL10, and CXCL11 production in keratinocytes by activating NF‐κB, STAT1, or IRF‐1 through PI3 K/Akt and MEK/ERK pathways. These effects of IL‐18 may promote the infiltration of type 1 T cells into lesions with inflammatory dermatoses and amplify the skin inflammation. IL‐18 may act as a pro‐inflammatory cytokine in these dermatoses and thus is a candidate therapeutic target.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by T helper 2 cell (Th2)-shifted abnormal immunity, skin barrier impairment, and pruritus. The prevalence of AD in childhood is slightly higher in boys than in girls; after puberty, the sexual difference is reversed. The female preponderance in all generations exists in intrinsic AD with enhanced Th1 activity and nickel allergy, lacking increased serum IgE or filaggrin mutation. AD is often deteriorated before menstruation. We review the effects of sex hormones on immune responses and skin permeability barrier and propose possible hypotheses for the above phenomena. After puberty, the immune responses of patients are remarkably influenced by sex hormones. Estrogen and progesterone enhance the activities of Th2/regulatory T cell (Treg) but suppress Th1/Th17. Androgens suppress Th1/Th2/Th17 and induce Treg. The skin permeability barrier is fortified by estrogen but is impaired by progesterone and androgens. Dehydroepiandrosterone suppresses Th2 but enhances Th1. The amount of steroid sulfatase converting dehydroepiandrosterone sulfate to dehydroepiandrosterone is higher in women than in men, and thus, women might be more susceptible to the influence of dehydroepiandrosterone. The balance of modulatory effects of sex hormones on immune responses and skin barrier might regulate the course of AD.

Psoriasis is a chronic inflammatory skin disease characterized by accelerated tumor necrosis factor-α/interleukin-23/interleukin-17 axis, hyperproliferation and abnormal differentiation of epidermal keratinocytes. Psoriasis patients are frequently associated with obesity, diabetes, dyslipidemia, cardiovascular diseases, or inflammatory bowel diseases. Psoriasis patients often show unbalanced dietary habits such as higher intake of fat and lower intake of fish or dietary fibers, compared to controls. Such dietary habits might be related to the incidence and severity of psoriasis. Nutrition influences the development and progress of psoriasis and its comorbidities. Saturated fatty acids, simple sugars, red meat, or alcohol exacerbate psoriasis via the activation of nucleotide-binding domain, leucine-rich repeats containing family, pyrin domain-containing-3 inflammasome, tumor necrosis factor-α/interleukin-23/interleukin-17 pathway, reactive oxygen species, prostanoids/leukotrienes, gut dysbiosis or suppression of regulatory T cells, while n-3 polyunsaturated fatty acids, vitamin D, vitamin B12, short chain fatty acids, selenium, genistein, dietary fibers or probiotics ameliorate psoriasis via the suppression of inflammatory pathways above or induction of regulatory T cells. Psoriasis patients are associated with dysbiosis of gut microbiota and the deficiency of vitamin D or selenium. We herein present the update information regarding the stimulatory or regulatory effects of nutrients or food on psoriasis and the possible alleviation of psoriasis by nutritional strategies.