Induction of various cytokines and development of severe mucosal inflammation by cagA gene positive Helicobacter pylori strains.
BACKGROUND
Helicobacter pylori strains possessing the cagA gene are thought to induce interleukin 8 (IL-8) in gastric mucosa. However, it is still unclear whether a relation exists between the cagA gene and the expression patterns of cytokines other than IL-8.


OBJECTIVE
To investigate the relation between the cagA gene and the production of various cytokine proteins using an enzyme linked immunosorbent assay (ELISA).


METHODS
In 184 patients, the cagA gene was detected by polymerase chain reaction (PCR), and levels of production of IL-1 beta, IL-6, IL-7, IL-8, IL-10, and tumour necrosis factor alpha (TNF-alpha) in antral biopsy specimens were measured by ELISA.


RESULTS
Mucosal levels of IL-1 beta, IL-6, IL-8, and TNF-alpha were significantly higher in H pylori positive than in H pylori negative patients. Furthermore, the mucosal levels of IL-1 beta and IL-8 were significantly higher in specimens infected with cagA positive strains than in those infected with cagA negative strains. In H pylori positive patients, the mucosal level of IL-8 was closely correlated with that of IL-1 beta (p < 0.0001), and the mucosal level of IL-6 was closely correlated with that of TNF-alpha (p < 0.0001).


CONCLUSIONS
These findings suggest that the ability to induce cytokines differs among the strains; cagA+ strains induce various kinds of cytokines and may cause severe inflammation, whereas cagA- strains induce IL-8 and IL-1 beta only weakly and may cause only mild inflammation. However, as most patients infected with the cagA+ strains have gastritis, these strains may not be equivalent to ulcerogenic strains.
Yamaoka
Y
Y
Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Kita
M
M
Kodama
T
T
Sawai
N
N
Kashima
K
K
Imanishi
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics*; D015169:Colony Count, Microbial; D016207:Cytokines / Q000276:immunology*; D004415:Dyspepsia / Q000276:immunology / Q000382:microbiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology / Q000382:microbiology; D005756:Gastritis / Q000276:immunology / Q000382:microbiology; D005798:Genes, Bacterial / Q000235:genetics*; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000235:genetics*; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; C080866:cagA protein, Helicobacter pylori