THE EFFECT OF TOPICAL DRUGS ON THE LOCAL CONCENTRATIONS OF IL-5 AND MOMETASONE FUROATE IN CHRONIC POLYPOUS RHINOSINUSITIS

Long-term persistent inflammation is the main factor of pathogenesis in chronic polypous rhinosinusitis (CRSwNP).  Perspective subject of current clinical otorhinolaryngology is the modification of drugs containing topical glucocorticosteroids to increase local bioavailability, reduce the concentration of glucocorticosteroids, and reduce the local inflammatory response. The aim of the work was to evaluate the effect of urea, magnesium sulfate, mannitol on the concentrations of mometasone furoate and IL-5 in the polypous tissue of patients with CRSwNP. The study included 146patients with CRSwNP aged 18 to 62 years.  Biopsies of polypous tissue were taken during polypotomy. In liquids obtained by microdialysis of polypous tissues, mometasone concentrations were determined by high-performance liquid chromatography. Concentrations of cytokines IL-3, IL-4, IL-5 and IL-10 in blood serum and IL-5 in microdialysates of polypous tissue were measured by ELISA.  The average age of patients with CRSwNP was 42.9 ±7.2 years, among them men – 93 (63,69%), women – 53 (36,30%).). Clinical parameters the severity of the disease on the SNOT-22 scale in patients with CRSwNP significantly exceeded those in the control group (p≤ 0.05). The results of the biochemical analysis of microdialyzates of polypous tissue showed an increase in the content of Na+ ions in the resistant form of CRSwNP compared with the sensitive and dependent 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 154ng/ml in biological fluids after microdialysis. When urea solution is added to mometasone, Cmax increases to 198ng/ml. In the native nasal polypous tissue dialysate, IL-5 levels were 89±2.01 pg/ml. 2 hours after the addition of mometasone furoate, IL-5 concentrations decreased to 61± 3.5 pg / ml, after the addition of urea - 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 patients with CRSwNP significantly exceeded (on average more than three times) those in the control group (p≤0.05). There was a tendency to increase IL-3 and IL-4 (in 2 times) and to decrease IL-10 levels of in blood sera (by more than 1.5 times) in patients with CRSwNP compared with the control group. The results obtained help to develop new clinical approaches to increase the bioavailability of topical glucocorticosteroids, which allow to increase the effectiveness of basic therapy of CRSwNP and develop a treatment for the prevention of resistant forms of polyposis