Oa. Khair et al., EFFECT OF ERYTHROMYCIN ON HAEMOPHILUS-INFLUENZAE ENDOTOXIN-INDUCED RELEASE OF IL-6, IL-8 AND SICAM-1 BY CULTURED HUMAN BRONCHIAL EPITHELIAL-CELLS, The European respiratory journal, 8(9), 1995, pp. 1451-1457
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.