Effect of erythromycin on Haemophilus influenzae endotoxin-induced release of IL-6, IL-8 and sICAM-1 by cultured human bronchial epithelial cells

Although several studies have demonstrated that low-dose, long-term erythromycin treatment is effective in the management of patients with chronic lower respiratory tract infections, such as chronic bronchitis, bronchiolitis and bronchiectasis, the mechanisms underlying the action of erythromycin are not clear. We have cultured human bronchial epithelial cells (HBEC) as explant cultures from surgical tissue, and have investigated the effect of erythromycin on H. influenzae endotoxin (HIE)-induced release of inflammatory mediators in these cultures. Confluent epithelial cell cultures were incubated with 100 micrograms.mL-1 HIE +/- 0.1-10 micrograms.mL-1 erythromycin and were investigated for interleukin-6 (IL-6), interleukin-8 (IL-8) and soluble intercellular adhesion molecule-1 (sICAM-1) released into the culture medium after 24 h. HIE significantly increased the release of IL-6 from 3.9 +/- 1.5 pg.micrograms-1 cellular protein (in control untreated cultures) to 12.1 +/- 1.5 pg.micrograms-1 cellular protein, and IL-8 from 83.7 +/- 8.2 pg.micrograms-1 cellular protein (in control cultures) to 225.7 +/- 44.8 pg.micrograms-1 cellular protein. Similarly, HIE led to a significantly greater release of sICAM-1 from 0.04 +/- 0.01 ng.microgram-1 cellular protein, in control cultures, to 3.8 +/- 0.9 ng.microgram-1 cellular protein. Incubation of the epithelial cultures in the presence of 0.1-10 micrograms.mL-1 erythromycin significantly blocked the HIE-induced release of IL-6, IL-8, and sICAM-1, at all concentrations of erythromycin investigated. Erythromycin also attenuated neutrophil chemotaxis and adhesion to human endothelial cells, mediated by incubation with conditioned medium obtained from HIE-exposed epithelial cell cultures, in vitro. These results suggest that H. influenzae-induced release of inflammatory mediators from airway epithelial cells could contribute to chronic airway inflammation, and that this effect may be modulated by treatment with erythromycin.

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