PERIPHERAL-TYPE BENZODIAZEPINE RECEPTOR LIGANDS MODULATE HUMAN NATURAL-KILLER-CELL ACTIVITY

Following our earlier work, we evaluated the in vitro effect of ligand s active at the peripheral-type benzodiazepine receptors on human natu ral killer cell activity. Peripheral blood mononuclear cells were incu bated with benzodiazepine receptor ligands. After 4 h we observed a no nspecific inhibition of natural killer cell activity induced by both p eripheral (Ro5-4864 and PK 11195) and central (clonazepam) benzodiazep ine receptor ligands; after 24 h, the suppressive activity was specifi c to peripheral and mixed (diazepam) ligands, and the central-type lig and had no effect. This significant, specific suppression of NK cell a ctivity was completely reversed by the addition of human recombinant i nterleukin-2 or human leukocyte interferon. Our research provides addi tional information on the immunomodulatory effects of peripheral-type benzodiazepine ligands. Further studies are needed to clarify the unde rlying mechanism of natural killer cell inhibition and to determine th e clinical implications of these findings. (C) 1997 International Soci ety for Immunopharmacology.