Interleukin-8 controls bacterial transepithelial translocation at the costof epithelial destruction in experimental shigellosis

In shigellosis, the network of cellular interactions mediated by a balance of pro- and anti-inflammatory cytokines or chemokines is clearly tipped tow ard acute destructive inflammation of intestinal tissues by the bacterial i nvader. This work has addressed the role played by interleukin-8 (IL-8) in a rabbit model of intestinal invasion by Shigella flexneri. IL-8, which is largely produced by the epithelial cells themselves, appears to be a major mediator of the recruitment of polymorphonuclear leukocytes (PMNs) to the s ubepithelial area and transmigration of these cells through the epithelial lining. Neutralization of IL-8 function by monoclonal antibody WS-4 caused a decrease in the amount of PMNs streaming through the lamina propria and t he epithelium, thus significantly attenuating the severity of epithelial le sions in areas of bacterial invasion. These findings are in agreement with our previous work (31). In contrast to the PMNs, the bacteria displayed inc reased transepithelial translocation, as well as overgrowth in the lamina p ropria and increased passage into the mesenteric blood. By mediating eradic ation of bacteria at their epithelial entry site, although at the cost of s evere epithelial destruction, IL-8 therefore appears to be a key chemokine in the control of bacterial translocation.