Background: The purpose of this study was to assess the time-effect of clarithromycin on the inflammatory response in chronic rhinosinusitis (CRS), to further explore the use of macrolides in cell culture as a model for CRS, and its action on the immune system. Methodology: The time effect of clarithromycin on several cytokines was examined for IL-1β, IL-4, IL-5, IL-8 and GM-CSF. Samples prior and post-incubation were assessed, as well as samples collected 24h following removal of clarithromycin to determine if any immunomodulatory effect persisted. Cytokines were quantified using ProcartaPlexTM assays. Results: Of the 5 cytokines assessed, only IL-1β and IL-8 production were significantly inhibited at 4h. Increased levels of IL-4 were observed at 72 hours of incubation and returned to near baseline levels after its removal. IL-8 showed the most time-dependent relationship with clarithromycin. No differences between the expression of IL-5 and GM-CSF were found. Conclusions: The present work suggests a specific and dose-dependent impact of clarithromycin on the inflammatory response in CRS. Moreover, the immunomodulatory effects of clarithromycin on the cytokines IL-4 and IL-8 varied depending on length of exposure to clarithromycin. Further studies to further establish the relationship between length of exposure and cytokine expression, and with additional “actors” in CRS pathophysiology should be considered. This may enable us in the future to determine appropriate duration of macrolide therapy in patients with CRS.
Background Chronic rhinosinusitis (CRS) is a heterogeneous condition characterized by differing inflammatory endotypes. The identification of suitable biomarkers could enable personalized approaches to treatment selection. Objective This study aimed to identify and summarize clinical studies of biomarkers in adults with CRS in order to inform future research into CRS endotypes. Methods We conducted systematic searches of MEDLINE and Web of Science from inception to January 30, 2022 and included all clinical studies of adult CRS patients and healthy controls measuring biomarkers using enzyme-linked immunosorbent assays or Luminex immunoassays. Outcomes included the name and tissue type of identified biomarkers and expression patterns within CRS phenotypes. Study quality was assessed using the National Institutes of Health quality assessment tool for observational cohort and cross-sectional studies. A narrative synthesis was performed. Results We identified 78 relevant studies involving up to 9394 patients, predominantly with CRS with nasal polyposis. Studies identified 80 biomarkers from nasal tissue, 25 from nasal secretions, 14 from nasal lavage fluid, 24 from serum, and one from urine. The majority of biomarkers found to distinguish CRS phenotypes were identified in nasal tissue, especially in nasal polyps. Serum biomarkers were more commonly found to differentiate CRS from controls. The most frequently measured biomarker was IL-5, followed by IL-13 and IL-4. Serum IgE, IL-17, pentraxin-3 and nasal phospho-janus kinase 2, IL-5, IL-6, IL-17A, granulocyte-colony stimulating factor, and interferon gamma were identified as correlated with disease severity. Conclusion We have identified numerous potential biomarkers to differentiate a range of CRS phenotypes. Future studies should focus on the prognostic role of nasal tissue biomarkers or expand on the more limited studies of nasal secretions and nasal lavage fluid. We registered this study in PROSPERO (CRD42022302787).
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