Bronchial inflammation in acute bacterial exacerbations of chronic bronchitis: the role of leukotriene B4

Abstract

Neutrophils recruited to the airways in chronic obstructive pulmonary disease (COPD) are thought to mediate tissue destruction. Neutrophil recruitment is increased during bacterial exacerbations. The inflammatory process was studied in patients with an acute exacerbation of COPD in order to ascertain the role of leukotriene B 4 (LTB 4 ).The sputum of eight subjects with a bacterial exacerbation of COPD was analysed for neutrophil products (myeloperoxidase, elastase) and chemoattractants (interleukin-8 (IL-8) and LTB 4 ). The contribution of LTB 4 to the chemotactic activity of the sputum sol phase was determined using the LTB 4 receptor antagonist LY293111. The concentrations of the serum acute phase proteins a 1 -proteinase inhibitor, a 1 -antichymotrypsin and C-reactive protein were measured. All patients received appropriate broad-spectrum antibiotic treatment for 7±14 days.Initially, the sputum myeloperoxidase activity was high, indicating neutrophil influx; this was associated with high levels of IL-8 and LTB 4 . All these concentrations fell with treatment (p<0.01). The chemotactic activity of the sputum was raised on presentation and fell with treatment (p<0.01). LTB 4 contributed~30% of the total chemotactic activity on presentation; this diminished with therapy. All acute phase proteins were raised on presentation and fell with therapy (p<0.01).These findings suggest that leukotriene B 4 contributes to neutrophil influx into the airway in chronic obstructive pulmonary disease and may influence disease progresgression. Eur Respir J 2000; 15: 274±280.

New Concepts in the Pathobiology of Chronic Obstructive Pulmonary Disease

“…It is a potent chemoattractant for neutrophils and monocytes, and depending on the anatomical location, may contribute to the mobilization of these leukocyte populations into the lung. In some studies, the levels of IL-8 are increased in induced sputum of patients with COPD, and not surprisingly, the levels appear to correlate with the proportion of neutrophils (84), and are also increased in the sputum during exacerbations (85,86).…”

Role of T-lymphocytes and pro-inflammatory mediators in the pathogenesis of chronic obstructive pulmonary disease

“…As neutrophils comprise the predominant infl ammatory cell in COPD airspaces and, as noted earlier, lymphocytic infi ltrates within lung tissue per se are highly correlated with disease severity, it follows that IL-8 could play a part in the development of emphysema. IL-8 levels are increased in sputum of patients with COPD (Keatings et al 1996;Yamamoto et al 1997), and are further augmented during disease exacerbations, presumably in association with neutrophilic infl ammation triggered by bacteria (Crooks et al 2000;Aaron et al 2001;Gompertz et al 2001). Airway microbes induce IL-8 secretion by epithelial cells, and levels of this cytokine have been shown to correlate with airway bacterial load Patel et al 2002).…”

Animal Models of Chronic Obstructive Pulmonary Disease Exacerbations: A Review of the Current Status

“…In addition, even a stable COPD condition is associated with respiratory pathogens in the airways, which worsens airflow conductance [132,133] and triggers an inflammatory response [15,123,[134][135][136] and presence of inflammatory markers in sputum [133,[137][138][139]. During exacerbations, these inflammatory cells and mediators increase [140,141], as does the H 2 O 2 concentration in exhaled breath condensate [142,143].…”