Cytokines Induce an Epithelial Cell Cytokine Response

Abstract

Intravesical inoculation of gram negative bacteria or isolated bacterial products into mice induces an IL-6 response which can be measured within miutes of the infection.^1,2 In such infections, IL-6 is initially detected in the urine and subsequently in the serum. Similar IL-6 responses were found in human patients deliberately colonized in the urinary tract with E. coli Hu7343. IL-6 was secreted intermittantly into the urine in response to continuous bacterial infection in humans, but was not detected in serum. The rapid secretion of IL-6 into urine after bacterial stimulation, and the separation of local from systemic secretion in both humans and mice suggested that IL-6 was produced at the site of infection. Since epithelial cells dominate the naive urinary tract mucosal surface, we suggested that epithelial cells are one source of mucosally produced cytokines.⁴ Epithelial cell lines of urinary tract origin secrete IL-6 and IL-8, and can produce other cytokines after bacterial stimulation.^5–7 In this paper we demonstrate that epithelial cell lines of urinary tract origin can respond to exogenous cytokines. This response includes the up-regulation of a variety of cytokine mRNA species as well as secretion of IL-6 and IL-8. Furthermore, this response is specific to the stimulus used, with different cytokine mRNA species induced by different cytokine stimuli.