Review article: Immunological determinants that may affect the Helicobacter pylori cancer risk.
A large body of literature supports a role for Helicobacter pylori as an environmental factor which contributes to the development of gastric cancer through an intermediate stage of atrophic gastritis. The mechanism(s) by which H. pylori-associated chronic inflammation progresses to more serious diseases such as peptic ulcer and gastric cancer in certain individuals is not clear. Variations in the phenotype or genotype of the infecting H. pylori strain can play a role in the severity of disease. However, individuals infected with the 'more virulent' strains of H. pylori often never develop serious disease. Our experiments in inbred strains of mice provide evidence that host genetics also play a significant role in H. pylori-related gastritis. We have demonstrated that gastritis is dominated by a TH1 adaptive immune response, the degree of which directly correlates with the severity of disease. Treatment of mice with IL-12 or anti-IFN-gamma antibodies can increase or decrease, respectively the severity of gastritis in infected mice and adoptive transfer of TH1 cell lines significantly exacerbates disease. Thus, the tendency of an individual to respond to infection with specific immune mechanisms can dramatically affect the severity of disease and possibly put an individual at increased risk of progressing to disorders such as gastric cancer.
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
T G
TG
Blanchard
S J
SJ
Czinn
D000818:Animals; D005756:Gastritis / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D016481:Helicobacter Infections / Q000150:complications / Q000235:genetics / Q000276:immunology*; D016480:Helicobacter pylori / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000627:therapeutic use; D018664:Interleukin-12 / Q000276:immunology / Q000627:therapeutic use; D051379:Mice; D010641:Phenotype; D013274:Stomach Neoplasms / Q000209:etiology / Q000276:immunology*
D018664:Interleukin-12; D007371:Interferon-gamma