title: Cytokine expression pattern in benign prostatic hyperplasia infiltrating T cells and impact of lymphocytic infiltration on cytokine mRNA profile in prostatic tissue.
abstract: 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 microg; of IL-4 > 2 microg; and of IL-10 > 1 microg/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.
authors.affiliation: Department of Urology, University of Vienna Medical School, Vienna, Austria. georg.steiner@akh-wien.ac.at
authors.forename: Georg E
authors.initials: GE
authors.lastname: Steiner
authors.forename: Ursula
authors.initials: U
authors.lastname: Stix
authors.forename: Alessandra
authors.initials: A
authors.lastname: Handisurya
authors.forename: Martin
authors.initials: M
authors.lastname: Willheim
authors.forename: Andrea
authors.initials: A
authors.lastname: Haitel
authors.forename: Franz
authors.initials: F
authors.lastname: Reithmayr
authors.forename: Doris
authors.initials: D
authors.lastname: Paikl
authors.forename: Rupert C
authors.initials: RC
authors.lastname: Ecker
authors.forename: Kristian
authors.initials: K
authors.lastname: Hrachowitz
authors.forename: Gero
authors.initials: G
authors.lastname: Kramer
authors.forename: Chung
authors.initials: C
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Marberger
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics*; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008297:Male; D011467:Prostate / Q000166:cytology / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D018121:Receptors, Cytokine