Protective effect of nedocromil sodium on the interleukin-1-induced production of interleukin-8 in human bronchial epithelial cells

Abstract

Cellular constituents of the bronchial mucosa may participate in the recruitment of polymorphonuclear leukocytes to the inflamed airways through the generation of the neutrophil chemotactic peptide, interleukin-8 (IL-8). One important aspect of this interaction could be represented by the ability of pulmonary monokines, particularly IL-1, to induce gene expression of IL-8 in bronchial epithelial cells. In this study, we have evaluated the constitutive and IL-1-induced production of IL-8 by cultured human bronchial epithelial cells and examined the ability of the anti-inflammatory drug, nedocromil sodium, to inhibit the cytokine synthesis and release. Northern blot analysis demonstrated that IL-1 beta-treated human bronchial epithelial cells expressed appreciable levels of IL-8 mRNA during a period of 8 hours. This finding was associated with an increased release of immunoreactive IL-8 to the culture media, as assessed by specific ELISA. The bronchial epithelial cell-derived IL-8 demonstrated specific biologic activity, since the supernatants of stimulated bronchial epithelial cells possessed neutrophil chemotactic activity that could be inhibited by an antibody against human IL-8. Nedocromil sodium reduced the IL-1-induced release of IL-8 in a dose-dependent manner, but concentrations of the compounds, up to 10(-5) mol/L, did not affect the constitutive production of this cytokine.