title: Effect of TNF-α inhibitors on transcriptional levels of pro-inflammatory interleukin-33 and Toll-like receptors-2 and -9 in psoriatic plaques.
abstract: Tumor necrosis factor (TNF)-α inhibitors are considered to be effective in the treatment of psoriatic plaques, although the precise therapeutic pathway is not clear. Pro-inflammatory molecules, such as Toll-like receptor (TLR)-2 and -9 and interleukin (IL)-33, a member of the IL-1 receptor/TLR superfamily, have been found to be expressed in psoriatic plaques. The aim of the present study was to investigate whether TNF-α inhibitor treatment has an effect on the expression of IL-33 and TLR-2 and -9 in psoriatic plaques. Seventeen patients with psoriatic plaques were treated with a TNF-α inhibitor (etanercept or infliximab) for 12 weeks in an open-label study, and the transcriptional levels of IL-33 and TLR-2 and -9 were determined by reverse transcription-quantitative polymerase chain reaction in paired biopsies of psoriatic plaques obtained at baseline (B) and following the 12 weeks of treatment (P). The psoriasis area severity index (PASI) score was also determined. At B, elevated IL-33 and TLR-2 mRNA levels were observed in all cases, while TLR-9 showed elevated mRNA levels in 76% of cases. At P, reductions in the mRNA levels of IL-33, TLR-2 and TLR-9 were observed, with TLR-2 and -9 levels exhibiting significant reductions (P<0.0001, Wilcoxon signed-rank test). PASI scores were significantly reduced by the treatment (P<0.0001, Wilcoxon signed-rank test) and the changes in PASI scores exhibited a significant positive Pearson's correlation with the P/B mRNA expression ratios of TLR-2 or -9 in males (P<0.05), particularly in the etanercept group (P<0.0001). The findings support the efficacy of anti-TNF-α treatment on the innate immune response in psoriatic skin, with a focus on TLR-2 and -9 inhibition, suggesting their role in the pathogenic mechanism of plaque psoriasis, which may be associated with gender.
authors.affiliation: Department of Pathology, Medical School, University of Thessaly and University Hospital of Larissa, Larissa 41110, Greece ; Department of Surgery, Yale School of Medicine, New Haven, CT 06510, USA.
authors.forename: Dimitra P
authors.initials: DP
authors.lastname: Vageli
authors.affiliation: Department of Dermatology, Medical School, University of Thessaly and University Hospital of Larissa, Larissa 41110, Greece.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Exarchou
authors.affiliation: Department of Dermatology, Medical School, University of Thessaly and University Hospital of Larissa, Larissa 41110, Greece.
authors.forename: Efterpi
authors.initials: E
authors.lastname: Zafiriou
authors.affiliation: Department of Pathology, Medical School, University of Thessaly and University Hospital of Larissa, Larissa 41110, Greece.
authors.forename: Panagiotis G
authors.initials: PG
authors.lastname: Doukas
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, CT 06510, USA.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Doukas
authors.affiliation: Department of Dermatology, Medical School, University of Thessaly and University Hospital of Larissa, Larissa 41110, Greece.
authors.forename: Angeliki
authors.initials: A
authors.lastname: Roussaki-Schulze
keywords: Toll-like receptor-2; Toll-like receptor-9; anti-tumor necrosis factor-α; etanercept; infliximab; interleukin-33; mRNA; psoriatic plaques; quantitative polymerase chain reaction