Time-dependent effect of clarithromycin on pro-inflammatory cytokines in CRS

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.