Anti-inflammatory and immunomodulating effects of clarithromycin in patients with cystic fibrosis lung disease.
OBJECTIVE
Macrolide antibiotics are widely used in the treatment of suppurative lung diseases including cystic fibrosis (CF), the most common inherited fatal disease in the Caucasian population. This condition is characterized by secondary Pseudomonas infection resulting in neutrophil infiltration within the airways. The aim of the study was to investigate the evolution of inflammatory process in CF patients receiving long-term clarithromycin therapy.


METHODS
Twenty-seven CF patients (mean age, 12 years) were enrolled into the study. Beside the basic therapy the patients were treated with clarithromycin at a dose of 250 mg every other day orally. All patients were routinely examined every 3 months. Blood and sputum were collected before clarithromycin treatment and then again 3, 6 and 12 months after the drug prescription. Cytokine concentrations (tumor necrosis factor-alpha, interleukin-8, interleukin-4, interferon-gamma) in the sputum and plasma were assayed. Peripheral blood lymphocyte response to phytohemagglutinin was also evaluated.


RESULTS
Clarithromycin treatment resulted in a marked reduction of the cytokine levels both in the sputum and plasma specimens. At the same time, the interferon-gamma/interleukin-4 ratio has been significantly elevated. In addition, a sustained increase of peripheral blood lymphocyte response to phytohemagglutinin was demonstrated. These changes were associated with a significant improvement of the lung function.


CONCLUSIONS
The beneficial effect of the prolonged treatment of CF patients with a 14-membered ring macrolide antibiotic clarithromycin seems to be associated not only with down-regulation of the inflammatory response, but also with immunological changes including the switch from Th2 to Th1 type response.
Pukhalsky
Alexander L
AL
Research Center for Medical Genetics, Moscow, Russia. osugariver@medgen.ru
Shmarina
Galina V
GV
Kapranov
Nikolai I
NI
Kokarovtseva
Svetlana N
SN
Pukhalskaya
Daria
D
Kashirskaja
Natalia J
NJ
D000293:Adolescent; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002648:Child; D017291:Clarithromycin / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007249:Inflammation; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D012129:Respiratory Function Tests; D013183:Sputum / Q000737:chemistry
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D007155:Immunologic Factors; D017291:Clarithromycin