COMPARISON OF IMMUNOMODULATIVE EFFECTS OF HISTAMINE-2 RECEPTOR ANTAGONISTS IN GASTRIC-CANCER PATIENTS - FOCUS ON THE LYMPHOBLASTOGENESIS AND CYTOTOXICITY OF PERIPHERAL-BLOOD MONONUCLEAR-CELLS

A proposed mechanism of the immunomodulative effects of histamine-2 re ceptor antagonist (HZ-RA) has been considered to be the inhibition of suppressor T-lymphocyte activity, an increase in interleukin-2 product ion of helper T-lymphocytes, and an enhancement of natural killer cell activity. Since there is a lack of comparative data about the immunom odulative effects of various H2-RAs, cimetidine, ranitidine and famoti dine on peripheral blood mononuclear cells (PBMC), study of the compar ison of the actions of H2-RA will be required. We compared the immunom odulative effect of each H2-RA on PBMC in patients with gastric cancer . DNA synthesis, cytotoxicity of PBMC against K562 cells and gastric c ancer cell lines, and the levels of supernatant soluble interleukin-2 receptor (sIL-2R) were measured after the addition of each HZ-RA, resp ectively. Increased suppressor cell activities were attenuated and res tored to the levels of normal controls by the addition of cimetidine t o H2-RA. Statistically significant lymphoblastogenesis and cytotoxicit y against K562 cells were observed only in cimetidine-treated PBMC (P< 0.05). Such effects were not observed in ranitidine- or famotidine-tre ated PBMC. Neither cimetidine- nor ranitidine-activated PBMC showed an y significant cytotoxicity against gastric cancer cells. Significantly increased levels of sIL-2R were found in supernatants obtained from c ulture flasks treated with cimetidine or ranitidine and phytohemagglut inin (P<0.01). A significant correlation was found between the cytotox icity of cimetidine- or ranitidine-treated PBMC and supernatant sIL-2R (P<0.05). In conclusion, the most strongly modulative substance among H2-RAs was cimetidine and the least modulative drug was famotidine. T hese results might be due to their structural differences. The immunol ogical effects of H2-RA are unlikely to be mediated via specific inter action at the H2 receptor.