Influence of Allergy on the Immunomodulatory and Clinical Effects of Long-Term Low-Dose Macrolide Treatment of Nasal Polyposis

Abstract

Aims. Cytokine levels in nasal secretions reflect the inflammatory status of the nasal and paranasal sinus mucosa and the development of mucosal disease. The results of previous investigations suggest that macrolide antibiotics can be effective in treatment of chronic rhinosinusitis and nasal polyposis. The aim of this prospective study was to compare the immunomodulatory and clinical effects of long-term low-dose macrolide treatment of nonatopic and atopic patients with nasal polyposis.Methods. Forty (n = 40) patients with nasal polyposis, 22 allergic and 18 nonallergic were administered clarithromycin (CAM) 500 mg/day single oral dose for eight weeks. We measured the levels of proinflammatory Th1 cytokines TNF-α and IL-1β, Th2 cytokines IL-4, IL-5 and IL-6, and chemokine IL-8 in the nasal fluid samples, before and after treatment, using flow cytometric method. We also scored each of the 40 patients before and after therapy according to nasal symptom score and endoscopic score.Results. Following treatment, we found significantly reduced levels of IL-8 (p<0.01) and TNF-α (p<0.01) in nasal secretions in nonallergic patients. In subjects with nasal polyposis and allergy, we found decreased levels of IL-8 (p<0.01), IL-6 (p<0.05) and IL-1β (p<0.01). Macrolide therapy decreased the size of polyps in 45.45% of nonatopic and in 50% of atopic patients. After macrolide treatment, we found 67.83% patients in nonallergic group and 55.55% patients in allergic group with improved nasal symptoms.Conclusions. Long-term low-dose treatment with CAM was effective in the management of nasal polyposis. Our results showed that macrolide treatment of nasal polyposis have different immunomodulatory and similar clinical effects in allergic and nonallergic patients.

High and low doses of clarithromycin treatment are associated with different clinical efficacies and immunomodulatory properties in chronic rhinosinusitis

“…In agreement with our findings, Peric et al recently reported that a higherdose clarithromycin treatment (500 mg/day over eight weeks) decreased the size of nasal polyps in 45.45 per cent of non-atopic patients and in 50 per cent of atopic patients, demonstrating similar clinical effects in allergic and non-allergic patients. 21 • Low-dose, long-term clarithromycin has been recommended for treatment of chronic rhinosinusitis without nasal polyps • This study suggests short-term, high-dose clarithromycin is a more effective protocol • The anti-inflammatory properties of macrolides and consequent inhibition of Thelper type 2 inflammation are highlighted…”

Multi-analytical evaluation of serum levels of cytokines and adhesion molecules in patients treated for acute myeloid leukemia using biochip array technology

“…Altered levels of cytokines and adhesion molecules have been found in many pathological states and have been linked to many diseases such as autoimmune diseases, allergies, cardiovascular diseases and cancer [10][11][12][13][14][15] . The cytokine system constitutes an interacting functional network where the contribution from single cytokines is modulated by the levels of other cytokines.…”

Effects of Preoperative Clarithromycin Administration in Patients with Nasal Polyposis

“…Previous investigations performed by Perić et al (20,21) demonstrated that after eight weeks treatment by 500 mg single oral dose of clarithromycin daily, RANTES and IL-8 levels in nasal secretion samples fell in both allergic and non-allergic patients with nasal polyposis. Eosinophilic cationic protein (ECP) and tumour necrosis factor (TNF)-α levels fell in non-atopic patients, whereas IL-6 and IL-1β concentrations fell in atopic patients with nasal polyps (20,21). So, long-term, low-dose clarithromycin administration has similar anti-inflammatory and variable immunomodulatory effect in these patients.…”

“…In vitro roxithromycin administration directly suppresses IL-6 and RANTES production from cultured nasal polyp fibroblasts via the inhibition of IL-6 and RANTES messenger RNA expression (6). Previous investigations performed by Perić et al (20,21) demonstrated that after eight weeks treatment by 500 mg single oral dose of clarithromycin daily, RANTES and IL-8 levels in nasal secretion samples fell in both allergic and non-allergic patients with nasal polyposis. Eosinophilic cationic protein (ECP) and tumour necrosis factor (TNF)-α levels fell in non-atopic patients, whereas IL-6 and IL-1β concentrations fell in atopic patients with nasal polyps (20,21).…”

“…So, long-term, low-dose clarithromycin administration has similar anti-inflammatory and variable immunomodulatory effect in these patients. Interestingly, decreased levels of RANTES and IL-8, strong eosinophil and neurophil chemo-attractants, were associated with a reduction in polyp size in non-allergic and allergic patients (20,21). Matsune et al (22) demonstrated the ability of clarithromycin and roxithromycin to suppress vascular endothelial growth factor (VEGF) production from cultured nasal polyp fibroblasts, as well as VEGF messenger RNA expression.…”