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Paediatric Pulmonology and Allergology
2003 April, Vol. VI, No. 1 (pp.2178-2187)
Immunomodualtion in cystic fibrosis
Andrew Bush
Even early in the course of cystic fibrosis there is evidence of a bronchial inflammatory response, with increased interleukin (IL-8), neutrophils and neutrophil elastase in bronchoalveolar lavage. Neutrophils continue to be recruited to the airway, and worsen lung damage by the release of elastase and myeloperoxidase. Neutrophil elastase may actually serve to perpetrate infection by cleaving components of the host immune response, such as immunoglobulins and complement fragments. There is a wealth of in vivo and in vitro evidence that a variety of pro-inflammatory cytokines, in particular IL-8 and other neutrophil chemoattractants are down-regulated by macrolides. Macrolides reduce the ability of neutrophils to respond to chemotactic signals, reduce the release of potentially toxic mediators, and shorten neutrophil lifespan in the airway. Macrolides may inhibit protein synthesis by P.aeruginosa, may reduce bioflm formation and a possility to develop chronic infection in the airways; there is evidence of beneficial effects by antibiotic synergy in killing of multidrug resistant bacteria (claritromycine - tobramycine, azitromycine-cotrimoxazole, azytromicine-ceftazidime and azytromicine-doxycycline combinations). Three randomised, placebo controlled studies in three different continents, using different methods and different populations, have confirmed benefit for macorlides in cystic fibrosis. This paper reviews the current therapeutic options for immune modulation in cystic fibrosis, with the focus on the macrolide antibiotics in particular.