Comparison of immunomodulative effects of histamine-2 receptor antagonists in gastric cancer patients: Focus on the lymphoblastogenesis and cytotoxicity of peripheral blood mononuclear cells |
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| Institution: | 1. Department of Psychology, Royal Holloway, University of London, United Kingdom;2. Department of Experimental Psychology, University of Oxford, United Kingdom;3. School of Psychology, University of Birmingham, United Kingdom;1. Laboratory of Action and Body, Department of Psychology, Royal Holloway, University of London, Egham, Surrey, TW20 0EX, UK;2. Developmental Clinical Psychology Research Unit, Faculty of Psychology and Educational Sciences, 40, Bd du Pont d’arve, 1205 University of Geneva, Geneva, Switzerland;3. The Warburg Institute, Woburn Square, School of Advanced Study, University of London, London, WC1H 0AB, UK;1. Institute of Sport Science, University of Bern, Bremgartenstrasse 145, 3012 Bern, Switzerland;2. Priority Research Centre for Physical Activity and Nutrition, School of Education, University of Newcastle, Newcastle, Australia;3. School of Education/Early Start Research Institute, University of Wollongong, Wollongong, New South Wales, 2522, Australia;4. Department of Psychology, Education, and Child Studies, Erasmus University Rotterdam, 3062, PA, Rotterdam, the Netherlands |
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| Abstract: | A proposed mechanism of the immunomodulative effects of histamine-2 receptor antagonist (H2-RA) has been considered to be the inhibition of suppressor T-lymphocyte activity, an increase in interleukin-2 production of helper T-lymphocytes, and an enhancement of natural killer cell activity. Since there is a lack of comparative data about the immunomodulative effects of various H2-RAs, cimetidine, ranitidine and famotidine on peripheral blood mononuclear cells (PBMC), study of the comparison of the actions of H2-RA will be required. We compared the immunomodulative effect of each H2-RA on PBMC in patients with gastric cancer. DNA synthesis, cytotoxicity of PBMC against K562 cells and gastric cancer cell lines, and the levels of supernatant soluble interleukin-2 receptor (sIL-2R) were measured after the addition of each H2-RA, respectively. Increased suppressor cell activities were attenuated and restored to the levels of normal controls by the addition of cimetidine to H2-RA. Statistically significant lymphoblastogenesis and cytotoxicity against K562 cells were observed only in cimetidine-treated PBMC (P<0.05). Such effects were not observed in ranitidine- or famotidine-treated PBMC. Neither cimetidine- nor ranitidine-activated PBMC showed any significant cytotoxicity against gastric cancer cells. Significantly increased levels of sIL-2R were found in supernatants obtained from culture flasks treated with cimetidine or ranitidine and phytohemagglutinin (P<0.01). A significant correlation was found between the cytotoxicity 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. These results might be due to their structural differences. The immunological effects of H2-RA are unlikely to be mediated via specific interaction at the H2 receptor. |
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