Does Inflammation Mediate the Obesity and BPH Relationship? An Epidemiologic Analysis of Body Composition and Inflammatory Markers in Blood, Urine, and Prostate Tissue, and the Relationship with Prostate Enlargement and Lower Urinary Tract Symptoms.
Does Inflammation Mediate the Obesity and BPH Relationship? An Epidemiologic Analysis of Body Composition and Inflammatory Markers in Blood, Urine, and Prostate Tissue, and the Relationship with Prostate Enlargement and Lower Urinary Tract Symptoms.
复制标题
DOI：
10.1371/journal.pone.0156918
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Clark PE
中科院分区：
文献类型：
--
作者：
Fowke JH;Koyama T;Fadare O;Clark PE
前列腺增生症是一种与年龄和肥胖有关的常见疾病。然而，肥胖症和良性前列腺增生症之间的生物学途径尚不清楚。我们的目标是研究全身和前列腺组织炎症的生物标志物，作为肥胖和BPH相关性的潜在介体。参与者包括191名接受前列腺癌活检的非前列腺癌男性。训练有素的工作人员通过生物阻抗分析测量体重、身高、腰围和臀围，以及身体成分。用血清IL-6、IL-1β、IL-8和肿瘤坏死因子-α以及尿前列腺素E_2代谢物(PGE-M)、F2-异前列腺素(F2iP)和F2-异前列腺素代谢物(F2iP-M)来评价全身炎症反应。对前列腺炎性区域的分级、侵袭性、程度和位置进行评分，并对CD3和CD20阳性淋巴细胞进行染色。分析调查了多种身体成分分级、全身炎症和前列腺组织炎症与BPH结局的关系，包括超声下的前列腺大小和AUA症状指数(AUA-SI)的LUTS严重程度。前列腺大小与所有肥胖指标显著相关。例如，与体脂百分比、脂肪质量(Kg)或瘦质量(Kg)的第75个百分位数相比，男性的前列腺体积要大5.5到9.0mls。然而，前列腺大小与促炎细胞因子、PGE-M、F2iP、F2iP-M、前列腺组织炎症评分或免疫细胞浸润无关。相反，前列腺组织炎症的严重程度与LUTS显著相关，因此轻度炎症和重度炎症的男性之间的AUA-SI有7个点的差异(p=0.004)。此外，腰臀比(WHR)较大的男性明显更有可能患有严重的前列腺组织炎症(p=0.02)，在那些患有前列腺组织炎症的参与者中，高WHR与中度/重度LUTS显著相关(OR=2.56，p=0.03)。腰围比是对集中性肥胖的一种估计，它与前列腺组织炎症区域的严重程度以及患有炎症的男性下尿路综合征的严重程度有关。我们的结果表明，集中性肥胖会促进前列腺组织炎症，从而增加LUTS的严重程度。临床靶向的集中性脂肪沉积可能会降低LUTS的严重程度。从机制上讲，血或尿中的全身炎症或氧化应激标志物与前列腺大小或LUTS之间缺乏明确的关系，这表明除了全身炎症信号外，可能还有其他途径将身体肥胖与BPH结局联系起来。
BPH is a common disease associated with age and obesity. However, the biological pathways between obesity and BPH are unknown. Our objective was to investigate biomarkers of systemic and prostate tissue inflammation as potential mediators of the obesity and BPH association. Participants included 191 men without prostate cancer at prostate biopsy. Trained staff measured weight, height, waist and hip circumferences, and body composition by bioelectric impedance analysis. Systemic inflammation was estimated by serum IL-6, IL-1β, IL-8, and TNF-α; and by urinary prostaglandin E2 metabolite (PGE-M), F2-isoprostane (F2iP), and F2-isoprostane metabolite (F2iP-M) levels. Prostate tissue was scored for grade, aggressiveness, extent, and location of inflammatory regions, and also stained for CD3 and CD20 positive lymphocytes. Analyses investigated the association between multiple body composition scales, systemic inflammation, and prostate tissue inflammation against BPH outcomes, including prostate size at ultrasound and LUTS severity by the AUA-symptom index (AUA-SI). Prostate size was significantly associated with all obesity measures. For example, prostate volume was 5.5 to 9.0 mls larger comparing men in the 25th vs. 75th percentile of % body fat, fat mass (kg) or lean mass (kg). However, prostate size was not associated with proinflammatory cytokines, PGE-M, F2iP, F2iP-M, prostate tissue inflammation scores or immune cell infiltration. In contrast, the severity of prostate tissue inflammation was significantly associated with LUTS, such that there was a 7 point difference in AUA-SI between men with mild vs. severe inflammation (p = 0.004). Additionally, men with a greater waist-hip ratio (WHR) were significantly more likely to have severe prostate tissue inflammation (p = 0.02), and a high WHR was significantly associated with moderate/severe LUTS (OR = 2.56, p = 0.03) among those participants with prostate tissue inflammation. The WHR, an estimate of centralized obesity, was associated with the severity of inflammatory regions in prostate tissue and with LUTS severity among men with inflammation. Our results suggest centralized obesity advances prostate tissue inflammation to increase LUTS severity. Clinically targeting centralized fat deposition may reduce LUTS severity. Mechanistically, the lack of a clear relationship between systemic inflammatory or oxidative stress markers in blood or urine with prostate size or LUTS suggests pathways other than systemic inflammatory signaling may link body adiposity to BPH outcomes.