Activated BPH-T-cells abundantly express IL-17. The increase of IL-17 in BPH-tissues goes hand in hand with elevated levels of IL-15, a pro-inflammatory cytokine with T-cell growth factor properties. A clinical relevance of increased IL-17 expression under pathological conditions is suggested by the demonstration of significant upregulation of IL-6 and IL-8 production of prostatic SC by IL-17.

Chronic inflammation may induce an increased growth pattern of fibromuscular tissue in BPH similar to that of wound healing.

SUMMARY:The aim of the study is to characterize the type of immune response in benign prostatic hyperplasia (BPH) tissue.BPH tissue-derived T cells (n ϭ 10) were isolated, activated (PMA ϩ ionomycin), and analyzed for intracellular reactivity with anti-IFN-␥ and IL-2, -4, -5, -6, -10, and -13, as well as TNF-␣ and -␤ by four-color flow cytometry. Lymphokine release was tested using Th1/Th2 cytokine bead arrays. The amount of IFN-␥ and IL-2, -4, -13, and TGF-␤ mRNA expressed in normal prostate (n ϭ 5) was compared with that in BPH tissue separated into segments with normal histology (n ϭ 5), BPH histology with (n ϭ 10) and without (n ϭ 10) lymphocytic infiltration, and BPH nodules (n ϭ 10). Expression of lymphokine receptors was analyzed by immunohistology, flow cytometry, and RT-PCR. We found that 28 Ϯ 18% of BPH T helper cells were IFN-␥ ϩ /IL-4 Ϫ Th1 cells, 10 Ϯ 2% were IFN-␥ Ϫ /IL-4 ϩ Th2, and 12 Ϯ 6% were IFN-␥ ϩ /IL-4 ϩ Th0 cells. In relation, cytotoxic and double-negative BPH T lymphocytes showed a slight decrease in Th1 and Th0 in favor of Th2. In double-positive BPH T lymphocytes, the trend toward Th2 (35 Ϯ 15%) was significant (Th1: 12 Ϯ 7%; Th0: 5 Ϯ 4%). Lymphokine release upon stimulation was found in the case of IL-2, IL-5, IFN-␥, and TNF-␣ Ͼ 4 g; of IL-4 Ͼ 2 g; and of IL-10 Ͼ 1 g/ml. Expression of lymphokine mRNA in tissue was increased (2-to 10-fold) in infiltrated BPH specimens with and without BPH histology. The infiltrated BPH specimens with normal histology differed from those with BPH histology, most evident by the significant decrease in IFN-␥ and the increase in TGF-␤ mRNA expression. Infiltrated BPH specimens with BPH histology expressed significantly more IFN-␥ (5-fold), IL-2 (10-fold), and IL-13 (2.8-fold) when compared with noninfiltrated BPH specimens. BPH nodules, however, showed the highest level of expression of IL-4 and IL-13, with only intermediate levels of IFN-␥ and very low levels of IL-2 mRNA. Immune response in histologically less transformed BPH specimens is primarily of type 1, whereas in chronically infiltrated nodular BPH and especially within BPH nodules, it is predominantly of type 0 or type 2. (Lab Invest 2003, 83:1131-1146.

Overexpression of IL-15 and IL-15Ralpha-chain in BPH and massive proliferation of BPH-T-lymphocytes induced by IL-15 suggest a role for IL-15 in prostatic inflammation. Since IFN-gamma, a T-lymphocyte product, stimulates prostatic IL-15 production; chronic inflammation might be triggered by this paracrine loop.

No abstract