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

Abstract

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 1beta (IL-1beta) 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-1beta 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-1beta levels were low with cagA- and cagA+, cagE- H pylori infections.

Conclusions: The increase in antral IL-1beta 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.

Figure 1

Helicobacter pylori density in antrum and corpus. The end of the bars indicates the 25th and 75th percentiles. The 50th percentile (median) is indicated with a solid line in the box; the broken line indicates mean value. The 10th and 90th percentiles are indicated with error bars. DU, duodenal ulcer.

Figure 2

Relation between Helicobacter pylori density by culture and cellular infiltration in cagA+ cases. DU, duodenal ulcer; MNC, mononuclear cell; PMN, polymorphonuclear cell.

Figure 3

Mucosal interleukin (IL) 8 production. The end of the bars indicates the 25th and 75th percentiles. The 50th percentile (median) is indicated with a line in the box and the 10th and 90th percentiles are indicated with error bars. *Two cagA+ gastritis cases with extremely low in vitro IL-8 production, which indicate cagA positive, cagE, cagG negative strains. DU, duodenal ulcer.

Figure 4

Relation between mucosal interleukin (IL) 1β and IL-8 production and Helicobacter pylori density of cagA+ strains in the antrum.

Figure 5

Relation between mucosal interleukin (IL) 1β and IL-8 production and Helicobacter pylori density of cagA+ strains in the corpus.