Cytokine expression pattern in benign prostatic hyperplasia infiltrating T cells and impact of lymphocytic infiltration on cytokine mRNA profile in prostatic tissue

被引:153
作者
Steiner, GE
Stix, U
Handisurya, A
Willheim, M
Haitel, A
Reithmayr, F
Paikl, D
Ecker, RC
Hrachowitz, K
Kramer, G
Lee, C
Marberger, M
机构
[1] Univ Vienna, Sch Med, Dept Urol, A-1090 Vienna, Austria
[2] Univ Vienna, Sch Med, Dept Pathophysiol, A-1090 Vienna, Austria
[3] Univ Vienna, Sch Med, Dept Clin Pathol, A-1090 Vienna, Austria
[4] Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL USA
关键词
D O I
10.1097/01.LAB.0000081388.40145.65
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 = 10) were isolated, activated (PMA + ionomycin), and analyzed for intracellular reactivity with anti-IFN-gamma and IL-2, -4, -5, -6, -10, and -13, as well as TNF-alpha and -beta by four-color flow cytometry. Lymphokine release was tested using Th1/Th2 cytokine bead arrays. The amount of IFN-gamma and IL-2, -4, -13, and TGF-beta mRNA expressed in normal prostate (n = 5) was compared with that in BPH tissue separated into segments with normal histology (n = 5), BPH histology with (n = 10) and without (n = 10) lymphocytic infiltration, and BPH nodules (n 10). Expression of lymphokine receptors was analyzed by immunohistology, flow cytometry, and RT-PCR. We found that 28 +/- 18% of BPH T helper cells were IFN-gamma(+)/IL-4(-) Th1 cells, 10 +/- 2% were IFN-gamma(-)/IL-4(+) Th2, and 12 +/- 6% were IFN-gamma(+)/IL-4(+) 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 +/- 15%) was significant (Th1: 12 +/- 7%; Th0: 5 +/- 4%). Lymphokine release upon stimulation was found in the case of IL-2, IL-5, IFN-gamma, and TNF-alpha > 4 mug; of IL-4 > 2 mug; and of IL-10 > 1 mug/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-gamma and the increase in TGF-beta mRNA expression. Infiltrated BPH specimens with BPH histology expressed significantly more IFN-gamma (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-gamma 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.
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页码:1131 / 1146
页数:16
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