Could TNF-antagonists be a novel treatment strategy for BPH patients?

Abstract

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.

Keywords: autoimmune disease; benign prostatic hyperplasia; inflammation; therapy; tumor necrosis factor.

FIGURE 1. FIGURE 1: Model indicating the cellular changes in BPH compared to the normal prostate.

Chronic inflammation is present in the prostates of many BPH patients, where anti-inflammatory therapies, such as TNF-antagonists, may be beneficial.

FIGURE 2. FIGURE 2: Long-term changes associated with BPH in men.

This figure highlights classic changes in men during their lifetime, particularly those associated with the development of BPH. Potential drivers of prostatic changes and the relevant therapeutic interventions are listed.