Relationship between mucosal levels of Helicobacter pylori-specific IgA, interleukin-8 and gastric inflammation.

Mucosal IgA is important in local immune defence. Helicobacter pylori induces a specific IgA response in antral mucosa, but its immunopathology is unknown. Interleukin-8 (IL-8) has been suggested to be important in H. pylori-induced inflammation. Current information on the relationship between H. pylori-induced IgA and mucosal inflammation is limited. To investigate possible associations between mucosal-specific IgA, the toxinogenicity of H. pylori, mucosal levels of IL-8 and gastric inflammation, 52 endoscoped patients were studied. These comprised 28 patients with peptic ulcer and 24 with non-ulcer dyspepsia. Of these patients, 38 had H. pylori infection: 28 with peptic ulcer and 10 with non-ulcer dyspepsia. Antral biopsies were taken for histology, H. pylori culture and measurement of mucosal levels of IL-8 (pg/mg) and specific IgA (A450x1000) by ELISA. Mucosal H. pylori IgA was detectable in 35 out of 38 patients with H. pylori infection, with a median (interquartile) level of 220 (147, 531) units. There was no significant difference in mucosal levels of the IgA antibodies between patients infected with cytotoxin-positive or cagA-positive strains of H. pylori and those with toxin-negative or cagA-negative strains. The IgA levels in those patients with severe neutrophil infiltration were lower than in those with mild or moderate infiltration (P<0.05). There was a weak inverse correlation between antral mucosal IgA and IL-8 in infected patients (r=-0.36; P=0.04). H. pylori infection induced a significant local mucosal IgA response in most infected patients. The level of IgA antibodies does not appear to be correlated with the toxinogenicity of H. pylori. However, patients with severe active inflammation appear to have decreased levels of IgA. An inverse correlation between mucosal IL-8 and IgA may suggest that IL-8-induced inflammation compromises the mucosal IgA defence and renders the mucosa susceptible to further damage.

Relationship between mucosal levels of interleukin 8 and toxinogenicity of Helicobacter pylori.

AIM OF STUDY: To investigate if an association exists between in-vivo mucosal levels of IL-8 and bacterial expression of cytotoxin and cagA gene of H. pylori. METHODS: Seventy-two dyspeptic patients referred for endoscopy were studied, including 36 patients with peptic ulcer (PU) and 36 with non-ulcer dyspepsia (NUD). Biopsies were taken for histology, H. pylori culture and measurement of IL-8 by ELISA. To test the ability of H. pylori to produce cytotoxin (VacA), broth culture supernatants were assayed on Vero cells and vacuolation measured. PCR was used to detect the cagA gene of H. pylori. RESULTS: H. pylori was isolated in 52 of 72 patients studied. Among the 52 strains, 25 (49%) were VacA+ve/cagA+ve; 12 (23%) were VacA-ve/cagA-ve; the remaining 15 strains (28%) were either VacA+ve/cagA-ve or VacA-ve/cagA+ve. IL-8 levels (median (interquartile) pg/mg) in patients infected with VacA+ve (1.5 (0.64, 2.84)) or cagA+ve strains (1.25 (0.72, 2.34) were significantly higher than in those with VacA-ve (0.76 (0.4, 1.0)) or cagA-ve strains (0.5 (0.4, 1.5); p<0.05). The neutrophil infiltration score was also higher in patients infected with VacA+ve or cagA+ve strains than in those infected with VacA-ve or cagA-ve strains (p<0.05). CONCLUSION: VacA+ve/cagA+ve strains were associated with an enhanced production of mucosal IL-8 in vivo and correlated with a stronger infiltration of neutrophils. Enhanced mucosal production of IL-8 and its role in neutrophil chemotaxis and activation could be important in H. pylori-induced gastroduodenal inflammation and in the development of peptic ulcer disease.

Relationship between the mucosal production of reactive oxygen radicals and density of Helicobacter pylori in patients with duodenal ulcer.

OBJECTIVE: To investigate the associations between the mucosal production of reactive oxygen radicals (RORs) in the gastric antrum and duodenum, Helicobacter pylori density and duodenal ulcer (DU). PATIENTS: Forty-seven endoscoped patients, comprising 22 with DU and 25 non-ulcer subjects, were included in the study. METHODS: Antral and duodenal biopsies were taken for histology, Helicobacter pylori culture and measurement of chemiluminescence. Biopsies were homogenized and cultured on Columbia blood agar plate. Colonies of H. pylori were counted and bacterial density expressed as colony-forming units (cfu)/mg of biopsy. Chemiluminescence was measured by luminometry and the results expressed as millivolt (mV)/min/mg of biopsy, after subtraction of background count. RESULTS: Thirty-one of 47 (66%) patients had antral H. pylori and 6/47 (12.8%) had proven duodenal colonization. Increased chemiluminescence (median (interquartile)) was found in H. pylori-infected patients compared to those without H. pylori in antral (90.0 (26.0, 249.0) vs. 7.0 (0.0, 10.0), P<0.001) and duodenal mucosa (22.0 (10.0, 100.0) vs. -2.5 (-10.0, 0.0) P<0.001). A positive correlation was found between antral H. pylori density and chemiluminescence response in both the antrum (r=0.77) and duodenum (r=0.52). DU patients showed an increased chemiluminescence compared to those non-ulcer subjects with or without H. pylori infection in antrum (163.5 (44.5, 297.8) vs. 33.0 (8.7, 168.0) (P=0.046) vs. 2.7 (0.1, 10.0), P<0.01) and duodenum (45.0 (17.5, 100.0) vs. 15.0 (-1.25, 22.5) vs. -2.5 (-10, 0.0), P<0.01). CONCLUSION: Increased production of RORs in the antrum and duodenum was found to be related to antral H. pylori density and associated with duodenal ulceration. The association between antral H. pylori and ROR release in the duodenum may be important in the pathogenesis of duodenal ulceration.

Association of antral mucosal levels of interleukin 8 and reactive oxygen radicals in patients infected with Helicobacter pylori.

1. Helicobacter pylori infection is characterized by an infiltration of neutrophils in the gastric mucosa. Neutrophil activation is an important source of reactive oxygen radicals, which cause tissue damage. Studies have shown that in Helicobacter pylori-infected patients there is increased mucosal production of interleukin 8. However, the role of interleukin 8 in the Helicobacter pylori-related inflammatory process and its relationship with reactive oxygen radicals remains to be clarified. The aims of this study were to investigate if there is any association between antral mucosal levels of interleukin 8 and reactive oxygen radicals and their relationship to gastric antral inflammation. 2. Fifty-two patients referred for endoscopy were recruited into the study. Gastric antral biopsies were taken for histology, culture and measurement of interleukin 8 and chemiluminescence (measuring reactive oxygen radicals). Interleukin 8 was measured by ELISA and the result expressed as pg/mg biopsy. Luminol-enhanced chemiluminescence was measured as mV min-1 mg-1 biopsy. Antral inflammation was assessed by a pathologist in a blinded fashion. 3. Antral mucosal levels of interleukin 8 and reactive oxygen radicals were significantly higher in Helicobacter pylori-colonized mucosa than in Helicobacter pylori-negative mucosa. After the eradication of Helicobacter pylori in patients with duodenal ulcer the median values (ranges) of interleukin 8 and reactive oxygen radicals fell from 1.21 (0.10-2.40) to 0.65 (0.00-1.60) and from 110.0 (10.0-959.0) to 14.5 (0.0-85.0) respectively. There was a positive correlation between interleukin 8 concentration and chemiluminescence response in the antral mucosa (r = 0.72). A higher interleukin 8 concentration was associated with greater neutrophil infiltration (r = 0.72) and mononuclear cell infiltration (r = 0.55); the magnitude of the chemiluminescence response was also positively associated with neutrophil (r = 0.77) and mononuclear cell infiltration (r = 0.59). 4. Interleukin 8 concentration is associated with an infiltration of neutrophils and mononuclear cells and is correlated with the production of reactive oxygen radicals in antral gastric mucosa infected with Helicobacter pylori. These findings suggest that interleukin 8 may be important in attracting and activating phagocytes to release reactive oxygen radicals, thereby causing mucosal damage.