Desireddi Naresh V, Campbell Phillip L, Stern Jeffrey A, Sobkoviak Rudina, Chuai Shannon, Shahrara Shiva, Thumbikat Praveen, Pope Richard M, Landis J Richard, Koch Alisa E, Schaeffer Anthony J
Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
J Urol. 2008 May;179(5):1857-61; discussion 1861-2. doi: 10.1016/j.juro.2008.01.028. Epub 2008 Mar 18.
The chronic pelvic pain syndrome is characterized by pelvic pain, voiding symptoms and varying degrees of inflammation within expressed prostatic secretions. We evaluated the chemokines monocyte chemoattractant protein 1 (CCL2) and macrophage inflammatory protein-1alpha (CCL3) in expressed prostatic secretions to identify marker increases associated with inflammatory (IIIA) and noninflammatory (IIIB) chronic pelvic pain syndrome. In addition, chemokine levels were correlated with clinical pain as determined by the National Institutes of Health chronic prostatitis symptom index.
Expressed prostatic secretions were collected by digital rectal examination, and evaluated by enzyme linked immunosorbent assays for monocyte chemoattractant protein 1 and macrophage inflammatory protein-1alpha in 154 patients including controls (13), those with benign prostatic hyperplasia (54), chronic pelvic pain syndrome IIIA (37) and IIIB (50). Monocyte chemoattractant protein 1 and macrophage inflammatory protein-1alpha levels were compared between IIIA, IIIB and the control subgroups, and correlated against the chronic prostatitis symptom index and pain subscore using a Spearman test.
Mean levels of monocyte chemoattractant protein 1 in the control, inflammatory benign prostatic hyperplasia, noninflammatory benign prostatic hyperplasia, inflammatory chronic pelvic pain syndrome and noninflammatory chronic pelvic pain syndrome were 599.4, 886.0, 1,636.5, 3,261.2 and 2,272.7 pg/ml, respectively. Mean levels of macrophage inflammatory protein-1alpha in the control, inflammatory benign prostatic hyperplasia, noninflammatory benign prostatic hyperplasia, IIIA chronic pelvic pain syndrome and IIIB chronic pelvic pain syndrome were 140.1, 299.4, 238.7, 1,057.8 and 978.4 pg/ml, respectively. For each cytokine both chronic pelvic pain syndrome subtypes had statistically higher levels than the control group and patients with benign prostatic hyperplasia (p = 0.0002). Receiver operating curves using monocyte chemoattractant protein 1 levels greater than 704 pg/ml and macrophage inflammatory protein-1alpha greater than 146 pg/ml identified patients with chronic pelvic pain syndrome with an accuracy of 90% from control patients. Macrophage inflammatory protein-1alpha levels (p = 0.0007) correlated with the pain subscore of the chronic prostatitis symptom index while monocyte chemoattractant protein 1 (p = 0.71) did not.
Monocyte chemoattractant protein 1 and macrophage inflammatory protein-1alpha within the prostatic fluid in both chronic pelvic pain syndrome subtypes provide candidate future biomarkers for chronic pelvic pain syndrome. In addition, macrophage inflammatory protein-1alpha increase in expressed prostatic secretions provides a new marker for clinical pain in chronic pelvic pain syndrome patients. Given these findings prostatic dysfunction likely has a role in the pathophysiology of this syndrome. These chemokines may serve as effective diagnostic markers and modulators against the chemokines could provide an attractive treatment strategy in individuals with chronic pelvic pain syndrome.
慢性盆腔疼痛综合征的特征为盆腔疼痛、排尿症状以及前列腺分泌物中不同程度的炎症。我们评估了前列腺分泌物中的趋化因子单核细胞趋化蛋白1（CCL2）和巨噬细胞炎性蛋白-1α（CCL3），以确定与炎性（IIIA）和非炎性（IIIB）慢性盆腔疼痛综合征相关的标志物升高情况。此外，趋化因子水平与美国国立卫生研究院慢性前列腺炎症状指数所确定的临床疼痛相关。
通过直肠指检收集前列腺分泌物，并采用酶联免疫吸附测定法对154例患者（包括对照组13例、良性前列腺增生患者54例、慢性盆腔疼痛综合征IIIA患者37例和IIIB患者50例）的单核细胞趋化蛋白1和巨噬细胞炎性蛋白-1α进行评估。比较IIIA、IIIB和对照组亚组之间的单核细胞趋化蛋白1和巨噬细胞炎性蛋白-1α水平，并使用Spearman检验将其与慢性前列腺炎症状指数和疼痛子评分相关联。
对照组、炎性良性前列腺增生组、非炎性良性前列腺增生组、炎性慢性盆腔疼痛综合征组和非炎性慢性盆腔疼痛综合征组的单核细胞趋化蛋白1平均水平分别为599.4、886.0、1636.5、3261.2和2272.7 pg/ml。对照组、炎性良性前列腺增生组、非炎性良性前列腺增生组、IIIA慢性盆腔疼痛综合征组和IIIB慢性盆腔疼痛综合征组的巨噬细胞炎性蛋白-1α平均水平分别为140.1、299.4、238.7、1057.8和978.4 pg/ml。对于每种细胞因子，两种慢性盆腔疼痛综合征亚型的水平在统计学上均高于对照组和良性前列腺增生患者（p = 0.0002）。使用单核细胞趋化蛋白1水平大于704 pg/ml和巨噬细胞炎性蛋白-1α水平大于146 pg/ml的受试者工作曲线从对照患者中识别慢性盆腔疼痛综合征患者的准确率为90%。巨噬细胞炎性蛋白-1α水平（p = 0.0007）与慢性前列腺炎症状指数的疼痛子评分相关，而单核细胞趋化蛋白1（p = 0.71）则不相关。
两种慢性盆腔疼痛综合征亚型前列腺液中的单核细胞趋化蛋白1和巨噬细胞炎性蛋白-1α为慢性盆腔疼痛综合征提供了未来可能的生物标志物。此外，前列腺分泌物中巨噬细胞炎性蛋白-1α的升高为慢性盆腔疼痛综合征患者的临床疼痛提供了新的标志物。鉴于这些发现，前列腺功能障碍可能在该综合征的病理生理学中起作用。这些趋化因子可作为有效的诊断标志物，针对趋化因子的调节剂可能为慢性盆腔疼痛综合征患者提供有吸引力的治疗策略。
