Interleukin-18 exacerbates skin inflammation and affects microabscesses and scale formation in a mouse model of imiquimod-induced psoriasis

Abstract

Background:As a potent pro-inflammatory cytokine of the interleukin (IL)-1 family, IL-18 was elevated in early active and progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index (PASI). Although results from previous studies have established that IL-18 may aggravate psoriatic inflammation, the mechanisms of this process remain unknown. In this study, IL-18 knock out (KO) mice and wild-type (WT) mice were used to investigate the effects of IL-18 within a mouse model of psoriasis.Methods:WT and IL-18 KO mice were divided into four groups, including imiquimod (IMQ)-treated IL-18 KO group (n=11) and WT group (n=13) as well as their respectively gene-matched control mice (receiving vaseline; n=12). PASI scores were used to evaluate psoriatic lesions in IMQ-treated mice. Pathological features and dermal cellular infiltration were investigated by hematoxylin and eosin staining. The levels of psoriasis-related cytokines including IL-23, IL-17, IL-12, IL-1β, IFNγ, IL-15, IL-27, and IL-4 were tested by real-time polymerase chain reaction (PCR). The protein level of IL-1β, IL-27, CXCL1, and Ly6g were investigated by immunohistochemistry (IHC).Results:Acanthosis (98.46±14.12 vs. 222.68±71.10μm, P<0.01) and dermal cell infiltration (572.25±47.45 vs. 762.47±59.59cells/field, P<0.01) were significantly milder in IMQ-induced IL-18 KO mice compared with that in WT mice. IMQ-induced IL-18 KO mice manifested larger areas of Munro microabscesses (11,467.83±5112.09 vs. 4093.19±2591.88μm2, P<0.01) and scales (100,935.24±41,167.77 vs. 41,604.41±14,184.10μm2, P<0.01) as compared with WT mice. In skin lesions of IL-18 KO mice, the expressions of IL-1β, IL-4, and IL-27 were all significantly upregulated but IL-17 was decreased. Histologically, strong positive signals of Ly6g were observed within the epidermis of IL-18 KO mice but expressions of CXCL1 were decreased.Conclusions:IL-18 may exacerbate prominent inflammation and influence pathological features in IMQ-induced mouse model of psoriasis. IL-18 may upregulate pro-inflammatory cytokines and reduce protective cytokines, thus aggravating psoriatic inflammation. In addition, IL-18 may be involved in the formation of Munro microabscesses and scales.