Cyclosporin 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-1 alpha (IL-1 alpha) 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-1 alpha 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-1 alpha and TNF-alpha stimulated an IL-6 response in the two epithelial cell lines. The IL-1 alpha-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-1 alpha 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-1 alpha may play a role in the induction of trauma-associated CsA-insensitive IL-6 secretion.