Time course of IL1 and IL6 synthesis and release in human bronchial epithelial cell cultures exposed to toluene diisocyanate.

We have previously demonstrated that human bronchial epithelial cells release appreciable amounts of interleukin 1 (IL1) and interleukin 6 (IL6) when exposed to toluene diisocyanate (TDI) in vitro. TDI is an inflammatory and asthmogenic stimulus presumed to act at least in part through immunological mechanisms. The epithelial cell-derived IL1 and IL6 can promote T cell activation and proliferation in culture, and if this also happens in vivo they may contribute to the persistence of the inflammatory response of the bronchial mucosa observed in TDI-sensitive asthmatics. In this study, we confirmed the release of biologically active IL1 beta and IL6-like substances from bronchial epithelial cells exposed to isocyanates in vitro, and related the rate and the magnitude of the cytokine secretion with the pattern of IL1 beta and IL6 gene expression and the extent of epithelial cell injury. In the epithelial cell cultures exposed to TDI, there was a parallel, progressive increase in the expression of IL6 mRNA and in the secretion of IL6 protein between 48 hours and 6 days after exposure. By contrast, although increasing amounts of biologically active IL1 beta were detected in the supernatants of TDI-exposed epithelial cells throughout the 6-day period following exposure, augmented levels of IL1 beta mRNA were only evident 6 days after exposure, suggesting that TDI exposure might have initially affected the enzymatic cleavage of the intracellular IL1 beta precursor and the mechanisms which regulate the secretion of mature IL1 beta.