Comparison of immunomodulative effects of histamine-2 receptor antagonists in gastric cancer patients: focus on the lymphoblastogenesis and cytotoxicity of peripheral blood mononuclear cells

Int J Immunopharmacol. 1994 Dec;16(12):985-93. doi: 10.1016/0192-0561(94)90077-9.


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)

Publication types

  • Comparative Study

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Adult
  • Aged
  • Cytotoxicity, Immunologic / drug effects*
  • DNA / biosynthesis
  • Female
  • Histamine H2 Antagonists / pharmacology*
  • Histamine H2 Antagonists / therapeutic use
  • Humans
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Lymphocyte Activation / drug effects*
  • Male
  • Middle Aged
  • Receptors, Interleukin-2 / analysis
  • Stomach Neoplasms / immunology*


  • Adjuvants, Immunologic
  • Histamine H2 Antagonists
  • Receptors, Interleukin-2
  • DNA