Suppression of Natural Killer Cell Activity by FG 7142, a Benzodiazepine Receptor 'Inverse Agonist,'.

摘要

Natural Killer (NK) cells, in addition to being important in the defense against viral infections, play a key role in the body;s surveillance against neoplastic diseases. Both basic and clinical studies suggest that some forms of anxiety, environmental stress, and major depression are associated with suppression of NK cell activity. A dose-dependent (5-50mg.kg) suppression of natural killer (NK) cell activity was observed 2 h after administration of the benxodiazepine receptor inverse against FG 7142 (N-methyl-beta-carboline-3-carboxamide), and was still manifest 24 h later. Addition of FG 7142 (1-1000 nM) to the 4 h chromium 51 release assay did not affect NK cell activity . Pretreatment of mice with the benzodiazepine receptor antagonist Ro 15-1788 (10mg/kg blocked FG7142-induced suppression of NK cell activity, but had no effect when administered alone. The suppression of NK cell activity by FG 7142, a compound which produces a syndrome resembling stress or anxiety in both animals and man, provides further evidence that the central nervous system pathways subserved by the benzodiazepine/GABA receptor chloride channel complex ( supramolecular complex') may play a role in the modulation of immune function. Reprints. (AW)