Features of the bladder cytokine status in combined experimental models of vitamin D deficiency and chronic bacterial cystitis

Bratchikov O.I., Koryagin E.A.

Kursk State Medical University, Ministry of Health of Russia, Kursk, Russia

Introduction. Cytokine-mediated mechanisms play a substantial role in the pathogenesis of chronic bacterial cystitis. However, the design of the vast majority of previous studies has not taken into account the systemic nutritional and metabolic status of the subjects, which may independently affect cytokine metabolism and the parameters under investigation, irrespective of infection. Vitamin D has well-documented immunomodulatory and anti-inflammatory properties, and its deficiency is reliably associated with an increased risk of both the first episode of urinary tract infection (UTI) and recurrent UTIs. Nevertheless, the effect of vitamin D status on cytokine metabolism in the bladder during UTIs remains largely unexplored. Aim. To investigate the features of bladder cytokine status in experimental models of vitamin D deficiency and chronic bacterial cystitis. Materials and methods. The study was carried out in 20 sexually mature female albino rats. Following experimental induction of vitamin D deficiency, the animals were divided into two groups: a control group without vitamin D deficiency (n=10) and a main group with vitamin D deficiency (n=10). A model of recurrent chronic bacterial cystitis was subsequently induced in both groups. Cytokine status was assessed at both stages of the experiment by measuring tissue concentrations of secretory immunoglobulin A (sIgA), interleukin-8 (IL-8), and interleukin-10 (IL-10) in bladder homogenates using a solid-phase chromogenic enzyme-linked immunosorbent assay (sandwich ELISA). Statistical analysis was performed using Microsoft Excel spreadsheets and Statistica V10 (StatSoft Inc., USA) and SPSS Statistics V17 (USA) software packages. Results. The mean baseline tissue concentration of sIgA in the intact bladder of animals with vitamin D deficiency was significantly 1.4-fold lower than in the control group (p<0.001), whereas baseline IL-8 and IL-10 concentrations did not differ significantly between the groups (p>0.05). In the chronic bacterial cystitis model, the mean induced tissue concentrations of sIgA, IL-8, and IL-10 in the bladder of animals with vitamin D deficiency were significantly lower than in the control group by 2.5-fold, 1.7-fold, and 2.8-fold, respectively (p<0.001). Discussion. Vitamin D deficiency in the experimental model of chronic bacterial cystitis was associated with a substantial and significant reduction in local anti-infectious immunity and bladder immune reactivity. This was manifested by the development of a decompensated hypoergic infectious-inflammatory process in the bladder, which may represent one of the mechanisms underlying the increased risk of UTIs and their recurrence reported in the literature in the setting of vitamin D deficiency. Conclusion. Vitamin D deficiency may independently suppress local anti-infectious immunity and immune reactivity of the bladder both under normal conditions and following exposure to uropathogens. These findings support considering vitamin D as an important systemic regulator of the immunological mechanisms involved in chronic bacterial cystitis.

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About the Authors

Corresponding author: O.I. Bratchikov – Ph.D., MD, Professor, Academician of the Russian Academy of Natural Sciences, Head of the Department of Urology, Kursk State Medical University, Ministry of Health of Russia, Honored Doctor of the Russian Federation, Kursk, Russia; e-mail: bratov45@mail.ru

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