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 er ythromycin treatment is effective in the management of patients with c hronic lower respiratory tract infections, such as chronic bronchitis, bronchiolitis and bronchiectasis, the mechanisms underlying the actio n of erythromycin are not clear.We have cultured human bronchial epith elial cells (HBEC) as explant cultures from surgical tissue, and have investigated the effect of erythromycin on H. influenzae endotoxin (HI E)-induced release of inflammatory mediators in these cultures. Conflu ent epithelial cell cultures were incubated with 100 mu g . mL(-1) HIE +/-0.1-10 mu g . mL(-1) erythromycin and were investigated for interl eukin-6 (IL-6), interleukins (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 .mu g(- 1) cellular protein (in control untreated cultures) to 12.1+/-1.5 pg . mu g(-1) cellular protein, and IL-8 from 83.7+/-8.2 pg .mu g(-1) cellu lar protein (in control cultures) to 225.7+/-44.8 pg .mu g(-1) cellula r protein. Similarly, HIE led to a significantly greater release of sI CAM-1 from 0.04+/-0.01 ng .mu g(-1) cellular protein, in control cultu res, to 3.8+/-0.9 ng .mu g(-1) cellular protein. Incubation of the epi thelial cultures in the presence of 0.1-10 mu g . mL(-1) crythromycin significantly blocked the HIE-induced release of IL-6, IL-8, and sICAM -1, at all concentrations of erythromycin investigated. Erythromycin a lso attenuated neutrophil chemotaxis and adhesion to human endothelial cells, mediated by incubation with conditioned medium obtained from H IE-exposed epithelial cell culture, in vitro. These results suggest th at H. inflenzae-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.