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

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Author:: No author available

Journal Title:: Chinese Medical Journal

Issue:: 6

DOI:: 10.1097/CM9.0000000000000140

Key Word:: Interleukin-18;Psoriasis;Cytokines;Scales

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 ± 71.10 μm,P ＜ 0.01) and dermal cell infiltration (572.25 ±47.45 vs.762.47± 59.59 cells/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 ± 2591.88 μm2,P ＜ 0.01) and scales (100,935.24±41,167.77 vs.41,604.41 ± 14,184.10 μm2,P ＜ 0.01) as compared with WT mice.In skin lesions of IL-18 KO mice,the expressions of IL-1β3,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.

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