IL-22 and IL-17, signature cytokines of type 17 inflammation, as well as IL-4 and IL-13, signature cytokines of type 2 inflammation, both of which are positively correlated with the pathogenesis of psoriasis and allergic diseases, respectively, can induce expression of SCCA1/2 in airway epithelial cells and/or keratinocytes, leading to high expression of SCCA1/2 in these diseases.
Mean quantitative tissue mRNA expression of IFN-γ and IL-4 of patients with active and stable psoriasis were significantly lower than the controls (P < 0.001 and <0.01, respectively), but were not significantly different between active and stable psoriasis groups.
Furthermore, the therapeutic effect of anti-IL-4 receptor α against AD was not as high as that of IL-17 blockage against psoriasis, which implies a modification of the disease spectrum by non-Th2-type cytokine axes in AD.
We observed that IL-4 (rs2243250) had a reduced risk of psoriasis, while the IL-10 (rs1800871) conferred an increased susceptibility to psoriasis, as compared with controls.
As IL-4 therapy also improves psoriasis in humans and suppresses IL-23/T(H)17 responses without blocking IL-12/T(H)1, selective IL-4-mediated IL-23/T(H)17 silencing is promising as treatment against harmful inflammation, while sparing the IL-12-dependent T(H)1 responses.
Our data argue that IL-4 improves psoriasis not only via modification/induction of Th2 cells and type II dendritic cells, but also via direct inhibition of inflammatory cytokines in resident IL-4R-expressing epidermal cells and thereby alters the psoriatic skin phenotype toward a healthy skin phenotype.
In addition, a marked decrease in plasma IL-4 levels was observed in the psoriasis group, while no differences were observed with regard to levels of IFN-γ and Th2 between patients and normal subjects.
In the skin lesions, IL-17(+) cells were more represented in psoriasis than in AD, while the number of IL-4-producing cells was reduced in psoriasis patients than in AD ones.
Gene therapy for psoriasis in the K14-VEGF transgenic mouse model by topical transdermal delivery of interleukin-4 using ultradeformable cationic liposome.
Recently, the results of multiple well-powered genome-wide association studies have identified several additional loci outside the major histocompatibility complex region associated with psoriasis risk, including three genes involved in interleukin (IL)-23 signaling (IL-23R, IL-23A, IL-12B), two genes that regulate nuclear factor-kappaB signaling (TNIP1, TNFAIP3), and two genes involved in the modulation of T-helper type 2 immune responses (IL-4, IL-13).
The aim of this study was to assess whether other variants in the 5q31 region are causal to these SNPs or make independent contributions to psoriasis risk by genotyping a comprehensive set of tagging SNPs in a 725 kb region bounded by IL3 and IL4 and testing for disease association.
These results suggest that the genetic polymorphisms of IL-2 and IL-4 genes can be susceptible to psoriasis in Korean, especially late-onset psoriasis group.
These findings indicate that IL-4 and IL-13 have different regulatory effects on the expression of IL-13Ralpha1 and alpha2, and the overexpression of IL-13Ralpha1 may play some roles in the pathogenesis of chronic stage of AD or psoriasis.
To address this possibility, peripheral blood mononuclear cells (PBMC) isolated from patients with atopic dermatitis with the high serum IgE level, from those with psoriasis or from healthy volunteers were stimulated with recombinant IL-4 and analyzed for activation of transcription factors including activator protein (AP)-1 or signal transducers and activators of transcription (STAT)-6 by employing electrophoretic mobility shift assays.