ABSTRACT
INTRODUCTION: Psoriasis is a chronic inflammatory disease affecting the skin with an unclear etiological significance. AIM: In this study, we determined the mRNA expression and circulating levels of T helper (Th)/T regulatory (Treg) cytokines in psoriasis and analyzed their association with disease severity and treatment response. MATERIAL AND METHODS: 189 psoriasis patients and 189 controls were recruited. Circulating Th/Treg cytokines (IL-12, IFN-γ, IL-17, IL-23, TGF-ß and IL-4) were measured at baseline and at follow-up after 12 weeks of methotrexate treatment by ELISA and their relative mRNA expression at baseline was estimated by quantitative PCR. RESULTS: We observed increased levels of Th1/Th17 cytokines (IFN-γ, IL-17, IL-12 and IL-23) and a decrease in levels of Th2/Treg cytokines (IL-4 and TGF-ß) in psoriasis patients at baseline, as compared to controls. Further, we observed that there was a significant decrease in Th1/Th17 cytokines, whilst Th2/Treg cytokine levels were significantly increased on follow-up after treatment with systemic metho trexate, as compared to pre-treatment levels. Our results were further confirmed by the significantly higher mRNA expression of Th1/Th17 cytokine genes and significantly lower mRNA expression of Th2/Treg cytokine genes in patients with psoriasis, as compared to controls. A significant positive correlation of Th1/Th17 cytokines was observed with disease severity in cases, whilst Th2/Treg cytokines correlated negatively with disease severity. CONCLUSIONS: Our results show that increased Th1/Th17 cytokines and decreased Th2/Treg cytokines, both at the circulatory and gene expression level, play an important role in the immunopathogenesis and severity of psoriasis.
Subject(s)
Genetic Predisposition to Disease/epidemiology , Genetic Predisposition to Disease/genetics , Interferon-gamma/genetics , Interleukin-2/genetics , Polymorphism, Single Nucleotide/genetics , Psoriasis/epidemiology , Psoriasis/genetics , Adult , Age Distribution , Cohort Studies , Female , Genetic Markers/genetics , Humans , India/ethnology , Inflammation Mediators/immunology , Interferon-gamma/immunology , Interleukin-2/immunology , Male , Prevalence , Psoriasis/diagnosis , Risk Factors , Sex Distribution , Th1 Cells/immunologyABSTRACT
BACKGROUND: Psoriasis is known to be associated with an up-regulation of T-helper (Th)-1 & Th-17 cytokines and a relative down-regulation of Th-2 and T-regulatory (T-reg) cytokines. Certain allelic variants of these cytokine genes may alter Th1/Th17 and Th2/T-reg balance and may be associated with the risk of psoriasis. Hence we aimed to determine the association of IL-4 (rs2243250), IL-10 (rs1800871 and rs1800896) and FOXP3 (rs3761548) gene polymorphisms with risk of psoriasis in South Indian Tamils. METHODS: A total of 360 cases of psoriasis and 360 healthy controls were recruited. The polymorphism in IL-4 (rs2243250) & IL-10 (rs1800871) were typed by ARMS-PCR and IL-10 (rs1800896) & FOXP3 (rs3761548) were typed by TaqMan 5'allele discrimination assay. RESULTS: 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. However, IL-10 (rs1800896) and FOXP3 (rs3761548) gene polymorphisms were not associated with psoriasis risk. The plasma IL-4 levels was not different between the cases and controls, however the heterozygous CT genotype demonstrated significant high IL-4 levels. Plasma IL-10 levels were significantly increased in cases compared to controls, however none of the genotypes were associated with the plasma IL-10 levels. CONCLUSION: Our results suggest that IL-4 (rs2243250) polymorphism is protective against psoriasis, while IL-10 (rs1800871) polymorphism confers increased risk of psoriasis in South Indian Tamils. Detection of these genetic variants as predictive risk factors may lead to the selection of patient-tailored therapy to maximize the effectiveness of therapy.
