The influence of methotrexate on the gene expression of the pro-inflammatory cytokine IL-12A in the therapy of rheumatoid arthritis

Clinical and Experimental Rheumatology

Maria Kalipciyan¹  Robert M. Mader¹  Hans Bröll¹  Monika Mustak¹  Petra Högger¹  Eva-Luise Hobl¹  Ludwig Erlacher¹  Bernhard Duhm¹  Bernd Jilma¹ 

关键词: Methotrexate;    rheumatoid arthritis;    Rheumatoid arthritis;    methotrexate;    cytokines;    gene expression;    IL-12A;   

DOI  :  

学科分类：医学（综合）

来源: Pacini Editore SpA

【 摘 要 】

OBJECTIVES: Methotrexate (MTX) is a cornerstone in the treatment of rheumatoid arthritis (RA). Among its anti-proliferative activity, the anti-inflammatory mechanisms of MTX seem to play a major role in the treatment of RA. MTX reduces the production of pro-inflammatory cytokines such as interleukin (IL)-1, IL-2, IL-6 and interferon (INF)-γ, while the gene expression of anti-inflammatory Th2 cytokines like IL-4 and IL-10 is increased - altogether resulting in the anti-inflammatory effect. As little is known about the impact of MTX on other cytokines involved in the pathogenesis of RA, the present trial investigated the effect of MTX on IL-12A and IL-18 gene expression by peripheral blood mononuclear cells (PBMCs). For comparison, the effect on IL-6 and tumour necrosis factor (TNF) was analysed. METHODS: Using real-time PCR, mRNA concentrations of pro-inflammatory cytokines were determined in PBMCs from 17 patients before and during MTX therapy. Furthermore, gene expression was correlated with clinical and pharmacokinetic parameters such as methotrexate polyglutamate concentrations (Spearman`s correlation coefficient). To eliminate concomitant corticosteroids as confounding factor, a subgroup analysis for methotrexate without corticosteroids was performed in 6 patients. RESULTS: MTX statistically significantly reduced the mRNA expression of IL-12A by PBMCs in rheumatoid arthritis patients (Wilcoxon-test for paired samples, p

【 授权许可】

Unknown