CYCLOSPORINE-A DOES NOT INHIBIT IL-1-ALPHA-INDUCED EPITHELIAL-CELL IL-6 SECRETION

Trauma and infection activated a murine mucosal IL-6 response in different ways: the IL-6 response to bacteria was sensitive to Cyclosporin A (CsA); the IL-6 response to trauma was not. The aim of the present study was to identify possible activators of the CsA-insensitive IL-6 secretion at the epithelial cell level. Two human epithelial cell lines from the kidney (A498) and bladder (J82) were exposed to Escherichia coli Hu734, interleukin-1alpha (IL-1alpha) and tumour necrosis factor alpha. (TNF-alpha). The E. coli strain had been used for the in vivo experiments which led to this study, and IL-1alpha and TNF-alpha were likely to be released during infections and trauma. The secretion of IL-6 into the supernatants was compared between cells stimulated in the presence or absence of CsA. E. coli Hu734, IL-1alpha and TNF-alpha stimulated an IL-6 response in the two epithelial cell lines. The IL-1alpha-induced IL-6 response was rapid, and the secreted IL-6 levels were significantly higher than those induced by E. coli Hu734 or TNF-alpha. The IL-6 response to IL-1alpha was insensitive to CsA. By contrast, the IL-6 response to E. coli Hu734 and TNF-alpha was inhibited by CsA. These results demonstrated that the inhibitory effect of CsA depends on the stimulus triggering the IL-6 response. IL-1alpha may play a role in the induction of trauma-associated CsA-insensitive IL-6 secretion.