Rotavirus is the most important cause of severe gastroenteritis in children worldwide. We have investigated cytokine responses to rotavirus infection of cultured intestinal epithelial cells. Interleukin 8 (IL-8) is a chemotactic and cell-activating cytokine that is synthesized by epithelial cells and induced in response to bacterial enteric pathogens. Rotavirus inoculation increased IL-8 mRNA levels in cultured intestinal epithelial cells within 2 hr of infection. IL-8 secretion increased 10(2)- to 10(3)-fold by 8 hr postinfection. Secretion of TNF alpha or IL-1 beta, cytokines which themselves increase IL-8 secretion, was not induced by rotavirus, nor was that of TNF alpha, IFN alpha, IFN gamma, or IL-6. Neutralizing antibodies to TNF alpha or IL-1 alpha/beta did not affect the IL-8 response. Secretion of IL-8 was dependent on an intact viral capsid, as single-shell particles were inert. Neutralizing monoclonal antibodies (vp7-specific) that do not block cell attachment did block rotavirus stimulation of IL-8 secretion, indicating that attachment to the cell surface is not a sufficient stimulus to induce IL-8. Genetically inactivated rotavirus was also effective for IL-8 induction, indicating that viral replication was not required. These data suggest that epithelial cytokine IL-8 may be an important mediator of the host response to viral gastroenteritis pathogens such as rotavirus.