Peripheral-type benzodiazepine receptor ligands modulate human natural killer cell activity

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Abstract

Following our earlier work, we evaluated the in vitro effect of ligands active at the peripheral-type benzodiazepine receptors on human natural killer cell activity. Peripheral blood mononuclear cells were incubated with benzodiazepine receptor ligands. After 4 h we observed a nonspecific inhibition of natural killer cell activity induced by both peripheral (Ro5-4864 and PK 11195) and central (clonazepam) benzodiazepine receptor ligands; after 24 h, the suppressive activity was specific to peripheral and mixed (diazepam) ligands, and the central-type ligand had no effect. This significant, specific suppression of NK cell activity was completely reversed by the addition of human recombinant interleukin-2 or human leukocyte interferon. Our research provides additional information on the immunomodulatory effects of peripheral-type benzodiazepine ligands. Further studies are needed to clarify the underlying mechanism of natural killer cell inhibition and to determine the clinical implications of these findings.

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