Effect of topical drugs on the local concentrations of IL-5 and mometasone furoate in chronic polypous rhinosinusitis

Abstract

Long-term persistence of inflammation is the main factor of pathogenesis in chronic polypous rhinosinusitis (CRSwNP). Prospectives of current clinical otorhinolaryngology include modification of drugs containing topical glucocorticosteroids in order to increase local bioavailability, reduce the concentration of glucocorticosteroids, and alleviate the local inflammatory response. The aim of our work was to evaluate the effect of urea, magnesium sulfate, and mannitol on the concentrations of mometasone furoate and IL-5 in the polypous tissue of patients with CRSwNP. The study included 146 patients with CRSwNP aged 18 to 62 years. Biopsies of polypous tissue were taken during polypotomy. In the fluid samples obtained by microdialysis of polypous tissues, mometasone concentrations were determined by high-performance liquid chromatography. Concentrations of IL-3, IL-4, IL-5 and IL-10 cytokines in blood serum, and IL-5 in microdialysates of polypous tissue were measured by ELISA technique. The average age of patients with CRSwNP was 42.9±7.2 years, with prevalence of male patients (n = 93, 63.7%) over females (n = 53, 36.3%). Severity parameters of the disease by the SNOT-22 scale were significantly higher in CRSwNP patients than in control group (p ≤ 0.05). The results of biochemical analysis of microdialysates from polypous tissue showed increased content of Na+ ions in the resistant clinical cases of CRSwNP compared with the sensitive and dependent clinical forms (p < 0.05). Curves with the level of mometasone furoate were obtained in all the studied samples. It was found that the addition of magnesium sulfate solution to mometasone increases the Cmax of mometasone to 154 ng/mL in biological fluids after microdialysis. When urea solution is added to mometasone, Cmax increases to 198 ng/mL. In the native nasal polypous tissue dialysate, IL-5 levels were 89±2.01 pg/mL. Two hours after the addition of mometasone furoate, IL-5 concentrations decreased to 61±3.5 pg/mL, upon addition of urea, it changed to to 69±2.98 pg/mL (p ≤ 0.01, compared with the control without the addition of drugs). Analysis of serum cytokine levels showed that IL-5 concentrations in the patients with CRSwNP significantly exceeded (> 3-fold) those in the control group (p ≤ 0.05). There was a trend for increase of IL-3 and IL-4 (2-fold) and to decreased IL-10 levels in blood sera (> 1.5-fold) in patients with CRSwNP compared with controls. These results may be helpful for development of novel clinical approaches, in order to increase bioavailability of topically administered glucocorticosteroids, thus allowing to promote the effectiveness of basic therapy of CRSwNP and to develop therapy for the prevention of resistant forms of polyposis.