Inflammation and Oxidation Biomarkers in Patients with Cystic Fibrosis: The Influence of Azithromycin

Abstract

Objective: In addition to their antibiotic effect, macrolides appear to modulate the inflammatory response in cystic fibrosis (CF) and could influence oxidative stress. The objective of this study was to assess oxidation biomarkers and levels of inflammation and to determine whether there is an association between these parameters and the intake of macrolides. Materials and Methods:The subjects included in this cross-sectional study were, on the one hand, clinically stable patients with CF and, on the other, healthy controls. The following serum and plasma inflammatory and oxidative stress biomarkers were measured: interleukin-6 (IL-6), reactive C protein (RCP), tumor necrosis alpha (TNF-α), glutathione peroxidase (GPx), total antioxidant capacity (TAC), catalase (CAT), and superoxide dismutase (SOD), together with markers of lipid peroxidation (8-isoprostanes and thiobarbituric acid reactive substances [TBARS]). Clinical, anthropometric, lung function, radiological, and analytical variables (albumin, prealbumin, vitamins, and zinc) were also recorded. Results:We studied 36 adults with CF and 41 controls. No differences were observed in age, gender, or anthropometric variables. The patients had significantly higher levels of IL-6, TNF-α, RCP, TBARS, and isoprostanes, and lower levels of SOD than the controls. Twenty-three of the patients were treated with azithromycin, and they had more severe clinical and radiological parameters than those who were not but nevertheless presented significantly lower levels of TNF-α. No differences were observed in the markers of oxidation.Conclusion: Inflammation and oxidation biomarkers were increased in patients with CF compared with controls. The use of azithromycin was associated with reduced TNF-α levels and did not influence oxidation parameters.

Metabolomic Analysis by Nuclear Magnetic Resonance Spectroscopy as a New Approach to Understanding Inflammation and Monitoring of Pharmacological Therapy in Children and Young Adults With Cystic Fibrosis

“…However, results from a cross-sectional study, in which several markers of oxidative stress were measured and average duration of treatment with azithromycin was 38 ± 22 months, are not consistent with this explanation of our findings as levels of serum 15-F 2t -isoprostane, total antioxidant capacity, superoxide dismutase activity, catalase activity, glutathione peroxidase activity, and thiobarbituric acid reactive substances, in CF patients who had been taking azithromycin ( n = 23) and in CF patients who had not been receiving azithromycin ( n = 13) were similar ( Olveira et al, 2017 ). Nevertheless, differences in study design (cross-sectional vs. interventional) and biological matrices in which markers were measured (serum vs. EBC) make it difficult comparing this study and our study.…”

The Role of Specialized Pro-Resolving Mediators in Cystic Fibrosis Airways Disease

“…In contrast, some antibiotics have shown immunomodulatory properties ( Ruh et al, 2017 ) such as macrolides which suppress inflammatory cytokines ( Hoyt and Robbins, 2001 ; Amsden, 2005 ). Azithromycin has been particularly studied in CF and is routinely used for its immunomodulating effects, having shown to reduce exacerbation frequency and slightly improve lung function when taken continuously ( Bush and Rubin, 2003 ; Southern and Barker, 2004 ; Olveira et al, 2017 ). Of interest, while PMN counts and IL-8 levels decrease in CF patients’ sputum after antibiotic therapy, LXA4 levels significantly increase and are inversely correlated with IL-8 levels ( Chiron et al, 2008 ).…”

Ribosomal, Satellite III (1q12) and Telomere Repeat Copy Number Variations in Cystic Fibrosis Patients Used as a Model of Permanent Stress and Survivability

“…The sustained imbalance between oxidant and antioxidant species induces chronic inflammation. The role of oxidative stress in the progression of lung injury in the CF patients has been described [56, 57].…”