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The intestinal mucosa plays an active role in the response to inflammation, with increased pro-inflammatory mediator production. Intestinal epithelial cells are polarized and appear to represent an important component of the innate immune system, with a sophisticated response to inflammation from either the luminal or basolateral aspect of their environment. The manner in which the intestinal epithelial cell polarity affects their response to inflammatory stimuli is largely unknown. We hypothesized that polarized intestinal epithelial cells exhibit a directional inflammatory response dependent upon the location of inflammatory stimulus. Methods: Caco-2 cells, which exhibit characteristics of intestinal epithelial cells in culture, were plated on Transwell filters and allowed to fully differentiate, then treated with TNF-α (100ng/ml) or serum free media (SFM) in the apical or basolateral chamber. After 24 hours, production of the important chemokine IL-8 was determined in apical and basolateral media by ELISA. Results: Basolateral stimulation with TNF-α resulted in increased apical and basolateral IL-8 production (Figure 1). Basolateral IL-8 production significantly exceeded apical production (Figure 1). Apical TNF-α stimulation resulted in increased apical, but minimal basolateral IL-8 production (Figure 2). Conclusions: In the present study, polarized intestinal epithelial cells responded to TNF-α stimulation with focused directional secretion of the pro-inflammatory cytokine IL-8. These findings are important because they suggest that intestinal epithelial cells are capable of organizing their response to inflammatory signals and producing inflammatory mediators in a directed, vectorial fashion.