SJ Levine, T Benfield and JH Shelhamer
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1662, USA.

Interleukin-1 (IL-1) is an important proinflammatory cytokine which may contribute to the pathogenesis of inflammatory airway disorders, such as asthma and cystic fibrosis. Interleukin-1 receptor antagonist (IL- 1ra) is a naturally occurring IL-1 inhibitor which binds to IL-1 receptors without inducing agonist activity. Three IL-1ra isoforms have been identified: secreted IL-1ra (sIL-1ra), which is preferentially expressed by-inflammatory cells; intracellular IL-1ra (iIL-1ra) type I, which lacks a signal peptide and is preferentially expressed by epithelial cells; and iIL-1ra type II, which is identical to iIL-1ra type I except for the insertion of an additional 21 amino acids. The goal of this study was to assess whether airway epithelial cell iIL-1ra type I production can be regulated by corticosteroids. First, using reverse transcription-polymerase chain reaction (RT-PCR) and immunoblotting, we confirm that normal human bronchial epithelial (NHBE) cells and a human pulmonary mucoepidermoid carcinoma cell line (NCI-H292) express intracellular IL-1ra type I messenger RNA (mRNA) and protein. Second, using immunoblotting and ELISA, we report that dexamethasone induces time- and concentration-dependent increases in iIL-1ra type I protein within NCI-H292 cell lysates. Lastly, utilizing a ribonuclease protection assay, we report that dexamethasone induces concentration-dependent increases in iIL-1ra type I mRNA levels in NCI- H292 cells. These data suggest that corticosteroid-mediated induction of iIL-1ra type I mRNA and protein by human bronchial epithelial cells represents a novel mechanism by which IL-1-mediated airway inflammatory events might be regulated.

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