Relation between clinical presentation, Helicobacter pylori density, interleukin 1β and 8 production, and cagA status

Background - It is not known whether cagA+ Helicobacter pylori in duodenal ulcer (DU) have enhanced virulence compared with non-DU cagA+ H pylori. Aims - To investigate the relation between presentation, H pylori density, interleukin 1β (IL-1β) and IL-8 production, and cagA status. Methods - Fifty DU and 50 gastritis patients with cagA+ H pylori and 11 with cagA- infections were studied. Bacterial density and cytokine production were assessed using the same biopsies. Cytokine production was also measured from supernatants of medium following coculture of H pylori with MKN-45 cells. Results - There was no relation between H pylori density and cagA status. There was a dose dependent relation between mucosal cytokine levels and density of cagA+ H pylori. H pylori density increased to a threshold, followed by a rapid increase in cytokines and then a plateau. IL-1β and IL-8 levels in the antrum were greater in DU than in gastritis; in the corpus the cytokine level/H pylori differed irrespective of similar H pylori densities. However, cytokine production was similar in vitro, independent of presentation or biopsy site, suggesting that host factors are critical determinants of the inflammatory response. Mucosal IL-8 and IL-1β levels were low with cagA- and cagA+, cagE- H pylori infections. Conclusions - The increase in antral IL-1β and IL-8 production and inflammation in DU is related to increased numbers of bacteria and not to an increase in cytokine production per cagA+ isolate. There was no evidence of enhanced virulence of H pylori from DU compared with cagA+ non-DU H pylori.