Hypothesis / aims of study
Urinary tract infections (UTIs) is the most common bacterial infection among women. Prevention of relapse is a complex issue in the treatment of recurrent UTIs. It is generally accepted that the inflammatory process in the bladder wall persists even in the relapse-free period and is associated with increased apoptosis and urothelial dysfunction [1]. Standard antibacterial therapy courses allow to stop only the acute inflammatory process. We assumed that low molecular weight peptides of the bladder due to their known function regulation of apoptosis and inflammation will increase the duration of chronic cystitis remission [2]. To assess the mechanism of action of peptides and their effectiveness, we decided to use the assessment of the level cytokine/chemokines in urine before, during and after treatment.
Study design, materials and methods
The study involved 40 women with recurrent UTIs in accordance with the inclusion criteria: disease duration of more than 1 year, persistent imperative urge to urinate and frequent urination in the interrelapse period, normal general urine analysis values for at least 2 weeks, receiving treatment according to current clinical guidelines. As a therapy during the remission period, they received a bovine bladder peptide complex (Vezusten) 5 mg. intramuscularly 3 times a week, 10 doses in total.
Urine biospecimens were collected immediately before the first dose, 10 days after the start of peptide therapy and 21 days after the end of the course (42 days from the start of the study). Urine samples were frozen immediately after collection. The levels of the following cytokines and chemokines were measured: tumor necrosis factor (TNF-α), monocyte chemoattractant protein-1(MCP-1), IL-6, IL-8, macrophage migration inhibitory factor (MIF), regulated on activation, normal T-cell expressed and secreted (RANTES) using the enzyme-linked immunosorbent assay. Statistical analysis was performed using Statistica 6.0 software.
Results
Quantitative evaluation of urine cytokines and chemokines in the recurrent UTIs group in the remission period showed that the levels of cytokines IL-8, MCP-1, TNF-α, RANTES rose on the 10th day of bladder peptide complex treatment and fell 21 days after the end of treatment (p < 0.05). The biomarkers IL-8, MCP-1, TNF-α, RANTES decreased statistically significant both for the initial level and that on the 10th day of treatment. Changes in the levels of IL-6, MIF were not statistically reliable.
In addition, 21 days after the end of bladder peptide treatment the levels of RANTES and MCP-1 correlated with the duration of the relapse-free period, the lower the cytokine level, the longer the remission period (correlation coefficient = 0.51, p = 0.014)).
Interpretation of results
Increased levels of IL-8, MCP-1, TNF-α, RANTES in combination with normal urine tests after the start of peptide therapy may indicate the participation of these cytokines and chemokines in the therapeutic effect of bladder regulatory peptides in the bladder wall. The peptide complex action has a beneficial effect on the course of rUTIs and helps to increase the duration of the relapse-free period.
Our data indicate that bovine bladder peptides reduce the level of proinflammatory cytokines IL-8, MCP-1, TNF-α, RANTES in urine, probably due to the regenerative processes activation in the bladder wall in chronic cystitis. The levels of RANTES and MCP-1 biomarkers in urine can be considered as diagnostic and prognostic markers of therapy effectiveness and the duration of the relapse-free period. A decrease in biomarker levels after a course of treatment is a favorable prognostic factor.