OBJECTIVES: Chronic inflammation has been documented for years in benign prostatic hyperplasia (BPH), but only now has it become evident as a major factor in disease progression. This review highlights the immunologic key features of chronic inflammation in BPH and the present interpretation of these changes in the development and progression of BPH. RESULTS: Almost all BPH specimens show inflammatory infiltrates at histologic examination, but correlation to bacterial or other foreign antigens has not been established. Recognition of prostate secretion products by autoreactive T cells and animal models on experimental prostatitis demonstrate an autoimmune component to chronic inflammation. The infiltrate consists predominantly of chronically activated CD4(+) T lymphocytes, which are permanently recruited to prostate tissue via elevated expression of interleukin 15 (IL-15) and interferon gamma (IFN-gamma), proinflammatory cytokines produced by smooth muscle and T cells, respectively. With the appearance of infiltrates, T cell-derived cytokine production of IFN-gamma, IL-2, and transforming growth factor beta increases, the former two ultimately reaching 10-fold and the latter 2-fold higher levels in fully developed BPH than in normal prostates. As "mature" BPH nodules develop, IL-4 and IL-13 expression increases >2-fold, corresponding to a T-helper (Th)0/Th2 cytokine pattern. Dysregulation of the immune response in BPH may occur via elevated expression of proinflammatory IL-17, which stimulates a multifold production of IL-6 and IL-8, key executors of stromal growth in BPH. CONCLUSIONS: These data strongly suggest that BPH is an immune inflammatory disease. Unravelling the specific nature of immune dysregulation may help design novel drugs with these specific targets in mind.
OBJECTIVES: Chronic inflammation has been documented for years in benign prostatic hyperplasia (BPH), but only now has it become evident as a major factor in disease progression. This review highlights the immunologic key features of chronic inflammation in BPH and the present interpretation of these changes in the development and progression of BPH. RESULTS: Almost all BPH specimens show inflammatory infiltrates at histologic examination, but correlation to bacterial or other foreign antigens has not been established. Recognition of prostate secretion products by autoreactive T cells and animal models on experimental prostatitis demonstrate an autoimmune component to chronic inflammation. The infiltrate consists predominantly of chronically activated CD4(+) T lymphocytes, which are permanently recruited to prostate tissue via elevated expression of interleukin 15 (IL-15) and interferon gamma (IFN-gamma), proinflammatory cytokines produced by smooth muscle and T cells, respectively. With the appearance of infiltrates, T cell-derived cytokine production of IFN-gamma, IL-2, and transforming growth factor beta increases, the former two ultimately reaching 10-fold and the latter 2-fold higher levels in fully developed BPH than in normal prostates. As "mature" BPH nodules develop, IL-4 and IL-13 expression increases >2-fold, corresponding to a T-helper (Th)0/Th2 cytokine pattern. Dysregulation of the immune response in BPH may occur via elevated expression of proinflammatory IL-17, which stimulates a multifold production of IL-6 and IL-8, key executors of stromal growth in BPH. CONCLUSIONS: These data strongly suggest that BPH is an immune inflammatory disease. Unravelling the specific nature of immune dysregulation may help design novel drugs with these specific targets in mind.
Authors: Frank Rücker; Karin Lehrich; Axel Böhme; Mario Zacharias; Sascha A Ahyai; Jens Hansen Journal: World J Urol Date: 2021-01-24 Impact factor: 4.226
Authors: Kazutoshi Fujita; Charles M Ewing; Robert H Getzenberg; J Kellogg Parsons; William B Isaacs; Christian P Pavlovich Journal: Prostate Date: 2010-04-01 Impact factor: 4.104
Authors: Mehrnaz Gharaee-Kermani; Jose A Rodriguez-Nieves; Rohit Mehra; Chad A Vezina; Aruna V Sarma; Jill A Macoska Journal: Prostate Date: 2013-03-26 Impact factor: 4.104