Interleukin-1 Alpha Induced Release Of Interleukin-8 By Human Bronchial Epithelial Cells In Vitro: Assessing Mechanisms And Possible Treatment Options

Survival after lung transplantation is hampered by chronic lung allograft dysfunction (CLAD). Persistently elevated BAL-neutrophilia is observed in some patients despite treatment with azithromycin, which may be induced by IL-1 alpha. Our aim is to establish an in vitro model, assess mechanistic pathways and test different therapeutic strategies of IL-1 alpha-induced release of IL-8 by human bronchial epithelial cells. Bronchial epithelial cells (16HBE) were stimulated with IL-1 alpha with or without azithromycin or dexamethasone. IL-8 protein was analyzed in cell supernatant. Different MAP kinases (p38, JNK, ERK1/2, I kappa beta) and targets known to be involved in tumor formation (PI3K, Akt) were investigated. Finally, different treatment options were tested for their potential inhibitory effect. IL-1 alpha induced IL-8 in bronchial epithelial cells, which was dose-dependently inhibited by dexamethasone but not by azithromycin. IL-1 alpha induced p38 and Akt phosphorylation, but activation of these MAPK was not inhibited by dexamethasone. JNK, ERK1/2, I kappa b and PI3K were not activated. None of the tested drugs reduced the IL-1 alpha induced IL-8 production. We established an in vitro model wherein steroids inhibit the IL-1 alpha-induced IL-8 production, while azithromycin was ineffective. Despite using this simple in vitro model, we could not identify a new treatment option for azithromycin-resistant airway neutrophilia.