Influence of desmethylimipramine on natural killer cell activity

Mounting evidence suggests that the central nervous system (CNS) and the immune system are extensively interconnected. One question that arises is whether there is cross-reactivity between psychotropic agents, which are active in the CNS, and immune system function. To explore this notion, we examined the in vitro effect of the tricyclic antidepressant, desmethylimipramine (DMI), on human natural killer (NK) cell activity in seven separate experiments. At concentrations greater than or equal to 625 ng/ml, DMI reliably inhibited NK activity. Preincubation of lymphocytes with DMI before assay did not increase the inhibitory effect. Furthermore, removal of the drug from preincubated cells immediately before assay completely eliminated the inhibitory effect. These results demonstrate that DMI reversibly inhibits NK activity at serum concentrations that are not uncommonly found in depressed patients receiving this medication.