# Inflammatory Pathways in BPH/LUTS

> **NIH NIH R01** · ENDEAVOR HEALTH CLINICAL OPERATIONS · 2020 · $545,830

## Abstract

PROJECT SUMMARY/ABSTRACT
Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) is a common, complex and
poorly understood condition. Inflammation is strongly associated with increased LUTS severity and also with
the failure of medical treatment for BPH, resulting in progression to surgery. Despite this complexity, clinical
BPH treatment normally follows a scripted format using two medical approaches: α-adrenergic blockers (α-
blockers) to relax muscle tone and 5α-reductase inhibitors (5ARI) to shrink the prostate. Many men fail these
medical treatments, resulting in around 120,000 surgical interventions annually in the U.S. We have shown that
advanced human BPH has a profile of gene expression reminiscent of changes seen in autoimmune
inflammatory (AI) conditions such as rheumatoid arthritis (RA) and psoriasis. Data from a review of over
120,000 patient records demonstrated that BPH is positively correlated with the diagnosis of AI conditions, and
that treatment of AI conditions, specifically with TNFα antagonists, reduces subsequent BPH diagnoses. This
positively links BPH to other inflammatory conditions and shows that specific drug regimens used to treat these
diseases indicate avenues for BPH therapy. Loss of Th1/Th2 and Th17/Treg balance has been reported in
several inflammatory autoimmune diseases and may be responsible for the development and progression of
RA. Th1 and Th17 cells are implicated in many inflammatory conditions in humans and mice, while an
opposing anti-inflammatory role is attributed to Th2 and Treg cells. Likewise, our preliminary data show that the
M1/M2 macrophage balance changes to a more inflammatory phenotype as BPH progresses. M1
macrophages, in turn, drive Th1/Th17 polarization to maintain a proinflammatory state in the prostate. Mast
cells play a role in BPH and are also recognized mediators of the increase in inflammation seen in diseases
such as RA. We hypothesize that changes in the immune/inflammatory environment are major drivers of BPH
pathogenesis. The proposed work centers around this idea. We will define the immune/inflammatory
environment during human BPH progression to quantify changes relative to increases in Th1/Th2, Th17/Treg
and M1/M2 macrophage ratios as the disease progresses. We will then utilize a series of murine models to test
the consequences of manipulating the immune/inflammatory environment in relation to the cell types present,
as well as the intercellular signaling environment to test the premise that specific inflammatory cell or
associated chemokines can regulate prostate growth. The final aim will examine the role of current medical
approaches aimed at specific cytokine signaling pathways and determine whether these are effective at
reducing prostatic hyperplasia in a model of prostatic inflammation.

## Key facts

- **NIH application ID:** 9966996
- **Project number:** 5R01DK117906-03
- **Recipient organization:** ENDEAVOR HEALTH CLINICAL OPERATIONS
- **Principal Investigator:** Simon W Hayward
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $545,830
- **Award type:** 5
- **Project period:** 2018-09-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9966996

## Citation

> US National Institutes of Health, RePORTER application 9966996, Inflammatory Pathways in BPH/LUTS (5R01DK117906-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9966996. Licensed CC0.

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