Elevated Urine Levels of Macrophage Migration Inhibitory Factor in Inflammatory Bladder Conditions: A Potential Biomarker for a Subgroup of Interstitial Cystitis/Bladder Pain Syndrome Patients

Abstract

Objective: To investigate whether urinary levels of macrophage migration inhibitory factor (MIF) are elevated in interstitial cystitis/bladder pain syndrome (IC/BPS) patients with Hunner lesions and also whether urine MIF is elevated in other forms of inflammatory cystitis.

Methods: Urine samples were assayed for MIF by enzyme-linked immunosorbent assay. Urine samples from 3 female groups were examined: IC/BPS patients without (N = 55) and with Hunner lesions (N = 43), and non-IC/BPS patients (N = 100; control group; no history of IC/BPS; cancer or recent bacterial cystitis). Urine samples from 3 male groups were examined: patients with bacterial cystitis (N = 50), radiation cystitis (N = 18) and noncystitis patients (N = 119; control group; negative for bacterial cystitis).

Results: Urine MIF (mean MIF pg/mL ± standard error of the mean) was increased in female IC/BPS patients with Hunner lesions (2159 ± 435.3) compared with IC/BPS patients without Hunner lesions (460 ± 114.5) or non-IC/BPS patients (414 ± 47.6). Receiver operating curve analyses showed that urine MIF levels discriminated between the 2 IC groups (area under the curve = 72%; confidence interval 61%-82%). Male patients with bacterial and radiation cystitis had elevated urine MIF levels (2839 ± 757.1 and 4404 ± 1548.1, respectively) compared with noncystitis patients (681 ± 75.2).

Conclusion: Urine MIF is elevated in IC/BPS patients with Hunner lesions and also in patients with other bladder inflammatory and painful conditions. MIF may also serve as a noninvasive biomarker to select IC/BPS patients more accurately for endoscopic evaluation and possible anti-inflammatory treatment.

Figure 1

Urine MIF levels in all patient groups. A: Urine MIF concentration (pg/ml) in non-IC/BPS patients (control group) and IC/BPS patients with (IC/BPS-H) and without (IC/BPS-NH) Hunner lesions. Urine MIF was significantly elevated (#; p < 0.001) in IC/BPS-H patients. B: Urine MIF levels normalized to creatinine (MIF pg/mg Creat). IC/BPS patients with Hunner lesions also had significantly elevated (#; p <0.001) levels compared to non-IC/BPS patients. C; D: Urine MIF levels, either as concentration (pg/ml; C) or MIF normalized to creatinine (MIF pg/mg Creat) were significantly elevated (#; p < 0.001) in both patients with bacterial and radiation cystitis when compared to non-cystitis patients.

Figure 2

Receiver operating curve for urine MIF concentration (pg MIF/ml; A) and urine MIF normalized to creatinine (MIF pg/mg Creat; B). Area under the curve (AUC) presented with confidence intervals. Most appropriate cut-off point displayed along with sensitivity and specificity.