ROLE OF INFLAMMATION IN RESPIRATORY-TRACT INFECTIONS

In respiratory tract infections, leukocytes are recruited to the lungs , where they help remove invading organisms through phagocytic clearan ce. In some instances, however, the normal inflammatory response may b e as destructive as it is defensive. The neutrophils secrete a proteol ytic enzyme, neutrophil elastase, which has emerged as a major culprit in the pathogenesis of inflammatory airway disease. This enzyme has b een found to strip the bronchial epithelium, reduce ciliary beating, a nd stimulate excess mucus secretion, leading to mucus retention, bacte rial proliferation, and recurrent infections. Neutrophil elastase also stimulates epithelial cell interleukin-8 secretion and produces other chemoattractant cleavage products that lead to further neutrophil rec ruitment. It also impairs host defenses by damaging the major opsonoph agocytic receptor on the neutrophil and by weakening the efficacy of i mmunoglobulins. For this reason, an important goal in the treatment of respiratory tract infections should be to prevent or shorten the dura tion of neutrophil elastase release. A number of different approaches have been proposed or attempted in an effort to modulate the proteinas e burden. These include direct inhibition of elastase and interference with the recruitment, adherence, and degranulation of neutrophils. An even more fundamental approach would start in the bone marrow, where attempts might be made to modulate or modify neutrophil precursors so as to limit the destructive potential of the mature neutrophils.