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Differential Effects of Histamine Receptor Antagonists on Human Natural Killer Cell Activity

1987; Karger Publishers; Volume: 84; Issue: 3 Linguagem: Inglês

10.1159/000234431

1423-0097

Kristoffer Hellstrand, Svante Hermodsson,

Drug-Induced Adverse Reactions

In this study we investigated the modulation of natural killer (NK) cell activity by various histamine receptor antagonists in vitro. The histamine H₂-receptor antagonists cimetidine, ranitidine and tiotidine suppressed NK cell cytotoxicity (NKCC) at a high concentration (10^––³<i>M</i>). Cimetidine enhanced NKCC of Ficoll-Hypaque-separated lymphocytes and of lymphocytes enriched for NKCC by Percoll density gradient centrifugation. The enhancing effect of cimetidine was dose-dependent at final concentrations of 10^––4––10^––7<i>M</i> and did not require the presence of adherent cells/monocytes. Ranitidine did not affect NKCC over a wide range of concentrations. Tiotidine strongly enhanced NKCC of low-density, large granular lymphocyte-enriched mononuclear cells (MNC) in the presence of adherent cells/monocytes, but was ineffective in nonadherent effector cells. All H₂-receptor antagonists clearly antagonized histamine-induced NKCC enhancement in monocyte-containing effector cells. Clemastin, a specific H₁-receptor antagonist, effectively suppressed NKCC. This effect was mimicked by a clemastin isomer with very low affinity for H₁receptors. We conclude that (1) cimetidine enhances NKCC in vitro by a mechanism of action that is not specifically related to antagonism of H₂-receptors, (2) tiotidine displays mixed agonist/antagonist properties for MNC H₂-receptors and (3) NK-suppressive properties of clemastin are unrelated to H₁-receptor antagonism.