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Volume 6, Issue 6, pp. 65 - 67, June 2022

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This month in Cell Stress: TNF in benign prostatic hyperplasia (BHP). Image shows stylized false-color histology of BHP phenotype with immunohistochemical expression of p501s (bright areas) in prostate tissue (dark areas). Credit: Ming Yin, Rajiv Dhir and Anil V Parwani, CC BY 2.0 license via Wikimedia Commons. Image modified by Cell Stress. The cover is published under the CC BY 4.0 license.

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Microreviews

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

page 65-67 | 10.15698/cst2022.06.268 | Full text | PDF | 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.

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