OBJECTIVE Multiple sclerosis (MS) is a multifactorial chronic disease that affects the central nervous system (CNS). Toll-like receptors (TLRs) play a central role in cytokine production after pathogen- and danger-associated molecular patterns (PAMPs and DAMPs) and contribute to CNS damage in MS patients. Here, we evaluated the effects of interferon (IFN)-β treatment in TLR2 and TLR4-dependent cytokine production and mRNA expression in whole-blood cell cultures from MS patients. METHODS We evaluated cytokine production by ELISA from whole-blood cell culture supernatants and mRNA expression by real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMCs). RESULTS In patients treated with IFN-β, tumor necrosis factor (TNF)-α production after exposure to TLR2 agonist (Pam3Cys) was lower than in healthy controls and untreated MS patients. However, IFN-β treatment had no significant effect on TNF-α production after TLR4 agonist (LPS) stimulation. On the other hand, interleukin (IL)-10 production was increased in TLR4- but not in TLR2-stimulated whole-blood cell culture from MS patients under IFN-β treatment when compared to the controls. No differences in TNF-α or IL-10 mRNA expression in PBMCs from healthy controls and untreated or treated MS patients were detected, although PBMCs from treated patients presented higher levels of IL-32γ mRNA than those from controls. CONCLUSIONS Our data suggest that IFN-β treatment alters the TLR-dependent immune response of PBMCs from MS patients. This may contribute to the beneficial effects of IFN-β treatment.

中文翻译：

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干扰素-β治疗在多发性硬化症患者中差异性地改变TLR2和TLR4依赖性细胞因子的产生。

目的多发性硬化症（MS）是一种影响中枢神经系统（CNS）的多因素慢性疾病。Toll样受体（TLR）在病原体和危险相关分子模式（PAMP和DAMP）后，在细胞因子产生中起着核心作用，并在MS患者中造成CNS损害。在这里，我们评估了干扰素（IFN）-β治疗对MS患者全血细胞培养中TLR2和TLR4依赖性细胞因子产生以及mRNA表达的影响。方法我们通过ELISA评估了全血细胞培养上清液中细胞因子的产生以及实时聚合酶链反应在外周血单核细胞（PBMC）中的mRNA表达。结果在接受IFN-β治疗的患者中，暴露于TLR2激动剂（Pam3Cys）后，肿瘤坏死因子（TNF）-α的产生低于健康对照组和未经治疗的MS患者。但是，在TLR4激动剂（LPS）刺激后，IFN-β处理对TNF-α的产生没有显着影响。另一方面，与对照组相比，接受IFN-β治疗的MS患者经TLR4刺激的TLR4刺激的全血细胞培养物中白介素（IL）-10的产量增加，但没有增加。尽管健康人和未治疗或未治疗的MS患者的PBMC中的TNF-α或IL-10 mRNA表达均未检测到差异，但治疗后患者的PBMC的IL-32γmRNA水平高于对照组。结论我们的数据表明，IFN-β治疗改变了MS患者PBMC的TLR依赖性免疫应答。