Shift of the gastric T-cell response in gastric carcinoma.
OBJECTIVE
The etiology and pathophysiology of stomach carcinoma is complex, and the mechanism whereby H. pylori directly or indirectly induces carcinoma remains unclear. In this study, interleukin (IL)-8, IL-4 and interferon (IFN)-gamma were measured in the tissue culture supernatant of gastric organ cultures from subjects with chronic gastritis with or without H. pylori infection, and with or without gastric cancer and gastric dysplasia.


RESULTS
Interleukin-8 levels were higher in cancer- and H. pylori-infected gastritis subjects than in H. pylori-negative subjects (12.95 +/- 3.16, 10.48 +/- 1.55 and 4.49 +/- 1.28 ng/mL, respectively). Elevated levels of IFN-gamma were detected in both H. pylori-infected and non-infected subjects with uncomplicated gastritis (72.23 +/- 19.0 and 34.61 +/- 5.30 pg/mL) and in non-infected dysplasia subjects (88 +/- 20.5 pg/mL). Background levels of IL-4 (< or = 9.4 pg/mL) in uncomplicated gastritis subjects and relatively high levels of IL-4 in dysplasia subjects (25.8 +/- 7.3 pg/mL) were detected. In contrast, trace amounts of IFN-gamma (16.01 +/- 0.35 pg/mL) and high levels of IL-4 (42.81 +/- 8.49 pg/mL) in gastric biopsy culture supernatants were found in cancer subjects. Mucosal IL-4 levels (but not IL-8 levels) correlated with infection and mucosal anti-H. pylori immunoglobulin G antibody.


CONCLUSIONS
The significant differences between gastritis with and without cancer and dysplasia indicated a shift from a Th1 to a Th2 helper cell pattern of cytokine secretion. This study has identified a local mucosal defect in gastric cancer. The near absence of IFN-gamma production from the mucosa at the margins of the tumor may be a critical factor in promoting growth of neoplastic cells.
Ren
Z
Z
Discipline of Immunology and Microbiology, School of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Newcastle, NSW, Australia.
Pang
G
G
Clancy
R
R
Li
L C
LC
Lee
C S
CS
Batey
R
R
Borody
T
T
Dunkley
M
M
D000230:Adenocarcinoma / Q000209:etiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood; D005260:Female; D016481:Helicobacter Infections / Q000150:complications / Q000276:immunology; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000209:etiology*; D013601:T-Lymphocytes / Q000276:immunology*
D000907:Antibodies, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D016209:Interleukin-8; D015847:Interleukin-4; D007371:Interferon-gamma