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 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 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Hahm
K B
KB
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Lee
S I
SI
Chung
J P
JP
Kim
W H
WH
Kim
J H
JH
Park
I S
IS
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D005260:Female; D006635:Histamine H2 Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013274:Stomach Neoplasms / Q000276:immunology*
D000276:Adjuvants, Immunologic; D006635:Histamine H2 Antagonists; D015375:Receptors, Interleukin-2; D004247:DNA