PSEUDOMONAS-AERUGINOSA INFECTIONS IN PATIENTS WITH CYSTIC-FIBROSIS - NEW IMMUNOMODULATORY STRATEGIES

Pseudomonas aeruginosa is the most common cause of morbidity and mortality in patients with cystic fibrosis. The pathogenesis of the fatal pulmonary infections it causes is multifactorial. A number of immunomodulatory strategies are currently being developed to improve the welfare of cystic fibrosis patients. The overall aims of these therapies are to: (a) attenuate the pathogenic effects of the bacterium's immunoevasive arsenal and the host inflammatory response; (b) boost pulmonary immunity; (c) modify the host's mucosal abnormalities. The major and most promising strategies involve: (a) protease inhibitor therapy with alpha-antitrypsin, secretory leukoprotease inhibitor, or ICI 200800, a synthetic chloromethylketone antagonist; (b) anti-inflammatory therapy, using ibuprofen rather than prednisone; (c) immunomodulation of the activities of leukotriene B4, interleukins-1 and -8 or tumour necrosis factor-alpha (only experimental data are available); (d) hyperimmune immunoglobulin transfer; (e) vaccination with an anti-idiotype antibody mimicking the P. aeruginosa mucoid exopolysaccharide, or oral immunisation with mucoid P. aeruginosa antigens (only experimental data are available); (f) treatment with aerosolised recombinant human deoxyribonuclease-I (DNase) and other mucolytic agents. To date, only protease inhibitors, ibuprofen and DNase are available (or will be available in the very near future) to the physician caring for patients with cystic fibrosis. Until curative treatment becomes feasible, clinical trials investigating alternative immunotherapies must receive a high priority on the list of strategies that need to be developed in order to improve the prognosis of patients with cystic fibrosis.