Modulation by flunisolide of tumor necrosis factor-alpha-induced stimulation of airway epithelial cell activities related to eosinophil inflammation.

BACKGROUND

Tumor necrosis factor (TNF)-alpha, a proinflammatory cytokine involved in the pathogenesis of asthma, displays multiple functions on a variety of cells, including bronchial epithelial cells (BECs).

OBJECTIVE

To characterize in vitro changes induced by TNF-alpha on the function of BECs that may be related to eosinophilic inflammation and to evaluate their modulation by an inhaled corticosteroid, flunisolide.

METHODS

A normal human bronchial epithelial cell line (BEAS-2B) was incubated with TNF-alpha (10 ng/ml) to evaluate (a) intercellular adhesion molecule (ICAM)-1 expression and granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-5 release by BEAS-2B; (b) eosinophil adhesion to BEAS-2B; and (c) the modulation of these activities by flunisolide (0.1 to 10 microM).

RESULTS

Stimulation of BEAS-2 with TNF-alpha generated an increase in ICAM-1 expression (p = .0012), in GM-CSF and IL-5 release (p < .01), and in eosinophil adhesion to BEAS-2B, but this latter effect did not reach statistical significance. Flunisolide at all the tested concentrations effectively inhibited ICAM-1 expression and GM-CSF and IL-5 release (p < .05). The percent inhibition induced by the highest flunisolide concentration (10 muM) for the various BEAS-2B functions was 30%, 60%, and 70%, respectively. The effect of flunisolide appeared to be related to an inhibition of "TNF-alpha-induced" ICAM-1 expression and cytokine release with little or no involvement of the "constitutive" expression and release.

CONCLUSION

An increase in ICAM-1 expression in BECs was found to be induced by TNF-alpha and associated with enhancement of the constitutive secretion of GM-CSF and IL-5, cytokines related to eosinophilic inflammation. The ability of flunisolide to modulate these BECs activities appears to be mostly related to the inhibition of the "TNF-alpha-induced" responses.