Could TNF-antagonists be a novel treatment strategy for BPH patients?
Could TNF-antagonists be a novel treatment strategy for BPH patients?
复制标题
作者：
肿瘤坏死因子（TNF）被广泛认为是全身和局部炎症过程中的关键参与者。由于这种分子在驱动慢性和急性炎症中的关键作用，它是用于自身免疫性（AI）疾病患者的最早治疗靶点之一。虽然前列腺中的炎症通常被观察到，但该器官以前并没有被认为是与一些AI疾病相关的全身性炎症的靶点。在良性前列腺增生（BPH）患者中，慢性炎症很常见，免疫细胞在器官中占很大比例。炎症细胞的积聚可能是对初始损伤的反应和/或驱动BPH发病的因素。当然，炎症会限制现有药物治疗对这些患者的疗效。我们先前表明，进展到适应症特异性手术的患者的BPH组织中的基因表达模式与AI疾病中观察到的变化一致。最近，我们证明，与没有AI疾病的患者相比，AI疾病患者的BPH患病率增加了约50%。AI疾病患者的治疗，特别是用TNF拮抗剂，将BPH发病率降低回基线人群BPH诊断率，或在某些疾病中，低于基线人群BPH诊断率。用广谱抗炎甲氨蝶呤治疗AI疾病患者并没有引起这种诊断的减少。用TNF拮抗剂的全身治疗减少了来自两种前列腺增生小鼠模型以及人类患者的前列腺组织中的上皮增殖和巨噬细胞积累。这些研究表明，TNF是BPH患者的潜在治疗靶点。
Tumor necrosis factor (TNF) is widely recognized as a pivotal player in both systemic and local inflammatory processes. Due to the critical role this molecule has in driving both chronic and acute inflammation, it was among the earliest therapeutic targets utilized for patients with autoimmune (AI) diseases. While inflammation in the prostate is commonly observed, the organ has not previously been considered a target of systemic inflammation associated with some AI diseases. In patients with benign prostatic hyperplasia (BPH), chronic inflammation is common, and immune cells represent a significant proportion of cells in the organ. Accumulation of inflammatory cells may be a response to an initial insult and/or a factor in driving BPH pathogenesis. Certainly, inflammation can limit the efficacy of existing medical therapies in these patients. We previously showed that a pattern of gene expression in BPH tissues from patients who had progressed to indication-specific surgery was consistent with the changes seen in AI diseases. Recently, we demonstrated that patients with AI disease have an approximately 50% increase in BPH prevalence compared to patients without AI disease. Treatment of AI disease patients, specifically with TNF-antagonists, reduces BPH incidence back to, or in some diseases, below, the baseline population BPH diagnosis rate. Treatment of AI disease patients with the broad spectrum anti-inflammatory methotrexate did not elicit this reduction in diagnoses. Systemic treatment with TNF antagonists reduces epithelial proliferation and macrophage accumulation in the prostate tissues from two mouse models of prostatic hyperplasia as well as human patients. These studies suggest that TNF is a potential therapeutic target in BPH patients.