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

Natural Killer NK cells, in addition to being important in the defense against viral infections, play a key role in the bodys 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 10mgkg 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 benzodiazepineGABA receptor chloride channel complex supramolecular complex may play a role in the modulation of immune function. Reprints.