Effect of clarithromycin on nuclear factor-kappa B and transforming growth factor-beta in chronic rhinosinusitis.
OBJECTIVE
Long-term, low-dose macrolide therapy is effective in the treatment of chronic rhinosinusitis. It is believed that macrolide antibiotics produce this benefit through an anti-inflammatory effect. In this study, the effect of clarithromycin treatment on the expression of transforming growth factor (TGF)-beta and the key pro-inflammatory nuclear transcription factor, NF-kappa B, was examined in vitro and in vivo.


METHODS
In vitro: nasal mucosa was obtained from 10 patients with chronic sinusitis and was cultured for 24 hours in the presence of clarithromycin or control. Cellular expression of TGF-beta and NF-kappa B was determined by immunohistochemistry. In vivo: 10 patients with chronic rhinosinusitis were treated for 3 months with clarithromycin. Nasal mucosal biopsies were taken pre- and posttreatment. Cellular expression of TGF-beta and NF-kappa B was again determined by immunohistochemistry.


RESULTS
Clarithromycin, when applied to nasal biopsies in vitro, reduced cellular expression of TGF-beta and NF-kappa B. Nasal biopsies taken before and after clarithromycin treatment showed no differences in cellular expression of NF-kappa B or TGF-beta.


CONCLUSIONS
Clarithromycin can reduce cellular expression of TGF-beta and NF-kappa B when applied in vitro, but its action during clinical therapy is less clear. Clarithromycin is capable of inhibiting pro-inflammatory cytokines in vitro, and reductions of TGF-beta and NF-kappa B may represent additional mechanisms by which macrolides reduce inflammation in chronic airway disease. Discrepancies between the actions of clarithromycin on nasal biopsies in vitro and after clinical therapy warrant further investigation.
Wallwork
Ben
B
School of Biomolecular and Biomedical Science, Griffith University, Brisbane, Australia benwallwork@hotmail.com
Coman
William
W
Mackay-Sim
Alan
A
Cervin
Anders
A
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001706:Biopsy; D002478:Cells, Cultured; D002908:Chronic Disease; D017291:Clarithromycin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis*; D009297:Nasal Mucosa / Q000737:chemistry; D010254:Paranasal Sinus Diseases / Q000188:drug therapy / Q000378:metabolism*; D012852:Sinusitis / Q000188:drug therapy / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000032:analysis*
D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D016212:Transforming Growth Factor beta; D017291:Clarithromycin