| Summary: | Adenoma and adenocarcinoma of the stomach are related to precancerous states and considered as successive stages of disregeneratory process proceeding against a background of chronic inflammation relying on cytokine-producing function of immune cells.
Evaluation of cytokine-producing function of blood immunocompetent cells under the influence on polyclonal activators in patients with adenoma and adenocarcinoma of the stomach.
Materials and Methods: Peripheral blood of 56 patients including 32 patients with adenomas and chronic atrophic gastritis and 24 patients with adenocarcinoma of the stomach was taken before surgery and biopsy. Peripheral blood of 30 healthy individuals was used as a control. To assess the status of the gastric mucosa, concentrations of pepsinogen I and pepsinogen II were determined in addition to instrumental methods. Cytokine-producing capacity of blood cells was determined using a polyclonal activator (PA) composed of PHA (4 μg/ml), conA (4 μg/ml) and LPS (2 μg/ml). Concentrations of the following cytokines: IL-1β, IL- 1Ra, TNFα, IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, MCP-1, VEGF and IFNγ in the supernatant of blood cells were measured with enzyme-linked immunosorbent assay (ELISA). The index of polyclonal activators unfluence (IPAI) on cytokine production was calculated: IPAI = A/B, where A is cytokine production induced by PA, B-spontaneous cytokine production level.
Results: In patients with stomach adenomas, serum concentration of pepsinogen I and the pepsinogen I/pepsinogen II ratio were significantly lower compared with healthy individuals indicating the development of adenoma combined with gastric mucosa atrophy. Pepsinogen I concentration was in inverse correlation with the percentage of Ki-67 positive epithelial cells, which was also in inverse correlation with IPAI of IFNγ possessing antiproliferative action. In patients with stomach adenomas,the increased IPAI of receptor antagonist IL-1compared with the control was revealed, that could lead to inflammation incompleteness and its torpid course. In conjunction with IPAI, increase in IL-18 level stimulates proliferative processes and contributes to disregeneratory changes in the stomach epithelium. Direct correlation between the ability of blood cells to the produce IL-1Ra under the PA influence and the number of metastases in the regional lymph nodes as well as reverse correlation between IPAI of IL-2 and the number of low differentiated cells in the tumor were observed. In patient with stomach adenomas, degree of atrophy increases as the pepsinogen I/pepsinogen II ratio decreases, the ability of immune cells to produce IL-18 under the influence of PA stimulates proliferation of cells, including atypical.
Conclusion: Findings suggest the ability of blood cells to produce TNFα, IL-18 and IFNγ under the influence of polyclonal activators was higher in patients with stomach adenomas than in patients with stomach adenocarcinomas. In patients with adenocarcinomas the decline in the production of cytokines with both the proliferative and antiproliferative effects indicates radical changes in the cytokine-producing capability of immunocompetent cells when malignant neoplasm became mature.
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