TRICYCLIC ANTIDEPRESSANTS INHIBIT HUMAN NATURAL-KILLER-CELLS

The commonly used antidepressants imipramine, amitriptyline, and nortr iptyline were found to significantly inhibit human natural killer (NK) cell-mediated cytolysis in vitro and suppress the stimulation of NK c ells by IFN-gamma. This is a previously unrecognized biologic property of these drugs with psychotropic activity, Tricyclic antidepressants did not decrease effector-target cell conjugation formation, nor did t hey induce target cell resistance to NK lysis, indicating that the dru gs might interfere with the killing mechanism of the effector cells, K inetic data reveal that the drug interference is related to an early p ostbinding event in the activation of NK cells, Results also showed th at the inhibitory effect of tricyclic antidepressants on human NK cell activity occurred in parallel to an increase in intracellular cyclic GMP concentration, However, the attenuation in the cyclic GMP formatio n by methylene blue, a selective inhibitor of soluble guanylate cyclas e, was not accompanied by a corresponding increase in NK cell cytolyti c activity. It is suggested that the stimulation of cyclic GMP was not directly involved in the inhibitory effect of antidepressants on NK c ells and perhaps was a secondary phenomenon, This immune cell modulato ry property of tricyclic antidepressants seems to indirectly provide e vidence for the concept that human brain neurons and NK cells might sh are regulatory system(s). (C) 1996 Academic Press, Inc.