Ulcer recurrence: cytokines and inflammatory response-dependent process

H. pylori and nonsteroidal antiinflammatory drugs (NSAIDs) are important factors in the recurrence of peptic ulcer diseases. However, H. pylori-negative recurring ulcers can also be found in nonusers of NSAIDs. The aim of this paper is to review recent data pertaining to mechanisms of ulcer recurrence. Prostaglandin E2 generation is impaired in the tissues of the ulcer scar site and prostaglandin depletion induced by administration of indomethacin during the healing of experimental gastric ulcer predisposes to future ulcer recurrence. Therefore, the prostaglandin deficiency may impair the quality of ulcer healing and thus increase the likelihood of future ulcer recurrence. Persistent infiltration of polymorphonuclear cells is the most prominent finding in the gastric ulcer scar in rats treated with indomethacin. Concomitant administration of prostaglandin E1-analog with indomethacin attenuates inflammatory infiltration and reduces future ulcer recurrence. Therefore, the inflammatory responses at the ulcer scar site may be a key to the quality of ulcer healing. Recent clinical findings suggest a close relationship between the quality of ulcer healing, infiltration of neutrophils and mononuclear cells, and future ulcer recurrence. Gastroprotective drugs such as prostaglandin analogs and prostaglandin inducers improve the quality of ulcer healing and reduce future recurrence. Production of inflammatory cytokines is stimulated by ulcerogenic factors such as NSAIDs, stress, and H. pylori infection. Inflammatory cytokines such as interleukin-1beta and tumor necrosis factor-alpha cause recurrence of healed ulcer. Synthetic prostaglandin E2 inhibits recurrence as well as the production of the cytokines.