SALMONELLA-TYPHI STIMULATION OF HUMAN INTESTINAL EPITHELIAL-CELLS INDUCES SECRETION OF EPITHELIAL CELL-DERIVED INTERLEUKIN-6

Interleukin 6 (IL-6) is a multifunctional cytokine that has been shown to be associated with both systemic and tissue-specific responses wit hin the host. Moreover, IL-6 is produced by both lymphoid and nonlymph oid cells and has been identified as a growth-inducing, growth-inhibit ing, and differentiation-inducing factor for these cells. Recent studi es of uropathogenic and upper respiratory pathogens have suggested tha t epithelial cell-derived IL-6 plays a role in mucosal host-parasite i nteractions. Since many mucosal enteric pathogens enter the host throu gh the epithelial cells of the distal small intestine, a role for inte stinal epithelial cell-derived IL-6 in the initial interaction between bacteria and host might also be predicted. However, no studies to dat e have determined whether the interaction of any bacteria with the epi thelial cells that line the small intestine of the host can induce IL- 6. To address this issue, we have established an in vitro model to eva luate the capacity of the gram-negative bacterium Salmonella typhi to induce IL-6 in the small intestine epithelial cell line Int407 and in other intestinal epithelial cell lines. The results demonstrate that b oth wild-type and live, attenuated S. typhi vaccine strains induce sma ll and large intestine epithelial cells to secrete IL-6, and kinetic a nalysis suggests that IL-6 may be one of the earliest responses follow ing adherence and invasion of enteric organisms. Thus, these studies s uggest a physiologic role for epithelial cell-derived IL-6 in the init ial interactions between host and bacterium in the small intestine.