In Helicobacter pylori infection both bacterial and host factors contribute to gastroduodenal mucosal damage. Indirect damage will result from the persistent innate and specific inflammatory response induced by bacterial products and the alterations in gastric physiology associated with infection. Cytokines play a critical role in the initiation and modulation of gastrointestinal inflammation. The gastric epithelium, which secretes chemokines in response to H. pylori, has a role in initiating acute inflammation. Bacterial induction of epithelial chemokines such as IL-8 involves protein tyrosine phosphorylation and NF-kappaB activation. Multiple genes in the cag pathogenicity island are essential for induction of epithelial chemokines. In vivo infection with cag-positive strains is associated with increased mucosal chemokines and inflammatory responses. Th1 cell-mediated responses characterized by interferon-gamma-secreting effector cells are also associated with increased mucosal inflammation. Variations in the magnitude and characteristics of the host cytokine responses induced by H. pylori are considered important factors determining the degree of chronic inflammation.