BACTERIAL-INDUCED RELEASE OF INFLAMMATORY MEDIATORS BY BRONCHIAL EPITHELIAL-CELLS

This review focuses on bacterial induction and release of inflammatory cytokines and adhesion molecules by human bronchial epithelial cells, with special reference to Haemophilus influenzae, a pathogen commonly associated with chronic bronchitis, Studies investigating the mechani sms underlying bacterial colonization of the airways and bacterial-ind uced chronic airway inflammation have suggested that these are likely to involve localization of bacteria to the site(s) of infection in the respiratory tract and induction of a local airway inflammation result ing in the initiation of epithelial damage. We have hypothesized that the gross airway epithelial damage observed in chronic infective lung disease is an indirect consequence of proteolytic enzymes and toxic ox ygen radicals generated by large numbers of neutrophils infiltrating t he airways. Furthermore, the infiltration and activation of the neutro phils is a consequence of increased release of proinflammatory mediato rs from the host respiratory epithelium, induced by bacterial products , such as endotoxin, This hypothesis is based on cell adhesion molecul es studies which have demonstrated that the concentrations of circulat ing cytokines, Haemophilus influenzae such as interleukin (IL)-8 and t umour necrosis factor-alpha (TNF-alpha), which have profound effects o n neutrophil activity, are increased in endotoxaemia and that airway e pithelial cells are a rich source of these cytokines. Support for this hypothesis is provided by studies of cultured human bronchial epithel ial cells incubated either in the absence or presence of purified endo toxin preparations from nontypable and type b H. influenzae strains wh ich have demonstrated that these endotoxins lead to significantly incr eased expression and/or release of proinflammatory mediators, includin g IL-6, IL-8, TNF-alpha and intercellular adhesion molecule-1 (ICAM-1) . Treatment of the cells with steroids can downregulate the expression and/or release of these inflammatory mediators, Additionally, these s tudies have demonstrated that culture medium collected from endotoxin- treated cultures, 24 h after treatment, significantly increases neutro phil chemotaxis and adhesion to human endothelial cells in vitro.