Increased expression of lymphocyte‐derived cytokines in benign hyperplastic prostate tissue, identification of the producing cell types, and effect of differentially expressed cytokines on stromal cell proliferation

Abstract

BACKGROUND: Benign prostatic hyperplasia (BPH) frequently exhibit infiltration of CD4 +/CD45RO + memory‐T‐lymphocytes. Expression and impact of lymphocyte‐derived growth factors on prostatic stromal cell (PSC) growth were investigated. METHODS: Lymphokine synthesis in normal prostate tissues (n = 3), BPH‐tissues (n = 13), BPH‐derived T‐cells (n = 6), BPH‐derived epithelial cells (BPH‐EC) (n = 5), normal prostate‐derived (n = 3) and BPH‐derived stromal cell lines (BPH‐SC) (n = 6), and prostate cancer (CaP) lines (n = 3) was analyzed by RT‐PCR and Southern‐blotting. The effect of interleukin (IL)‐2, ‐4, ‐7, and interferon‐γ (IFN‐γ) on normal and BPH‐SC growth was investigated by 3 H‐thymidine incorporation assays. RESULTS: All BPH‐tissues and, to a lesser degree, normal prostates, expressed significant amounts of IFN‐γ mRNA. However, only BPH‐tissues contained IL‐2 and IL‐4 mRNA (ratio: 10:13). BPH‐T‐cell lines were heterogenous in composition and expressed significant amounts of IFN‐γ, IL‐2, and IL‐4 mRNA. Low level expression of these lymphokines was also observed in BPH‐EC, CaP lines, and PSC lines. IL‐2, ‐7 and IFN‐γ stimulated the proliferation of BPH‐PSC lines but not that of normal PSC, while IL‐4 inhibited BPH‐PSC growth. CONCLUSIONS: Chronic inflammation may induce an increased growth pattern of fibromuscular tissue in BPH similar to that of wound healing. Prostate 52: 43–58, 2002. © 2002 Wiley‐Liss, Inc.