Monocyte chemoattractant protein-1 and macrophage inflammatory protein-1alpha as possible biomarkers for the chronic pelvic pain syndrome

Abstract

Purpose: 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.

Materials and methods: 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.

Results: 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.

Conclusions: 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.

Figure 1

a – Monocyte chemoattratant protein (MCP-1) levels in expressed prostatic secretions (EPS) of controls, inflammatory benign prostatic hyperplasia (BPH), non-inflammatory BPH, chronic pelvic pain syndrome with inflammation (CPPS IIIA) and chronic pelvic pain syndrome without inflammation (CPPS IIIB). The lower limit of detection, as determined by the lowest detectable assay standard by ELISA assay is 15.6 pg/ml. Error bars show standard error. * - indicates statistically significant difference b – Macrophage inflammatory protein (MIP-1α) levels in expressed prostatic secretions (EPS) of controls, inflammatory benign prostatic hyperplasia (BPH), non-inflammatory BPH, chronic pelvic pain syndrome with inflammation (CPPS IIIA) and chronic pelvic pain syndrome without inflammation (CPPS IIIB). The lower limit of detection, as determined by the lowest detectable assay standard by ELISA assay is 15.6 pg/ml. Error bars show standard error. * - indicates statistically significant difference c – MCP-1 and MIP-1α levels in the serum of CPPS IIIA, CPPS IIIB, and control patients.

Figure 2

Receiver operating curve (ROC) to discriminate IIIA/IIIB patients from control patients in our cohort employing MCP-1 cutpoint of 704 pg/ml and MIP-1α cutpoint of 146 pg/ml (Area under ROC curve – 0.892)

Figure 3

Spearman correlation between CPSI pain sub-score and MIP-1α levels.