Antidepressants augment natural killer cell activity: In vivo and in vitro

Depressed mood has been associated with reduced natural killer cell activit y (NKCA). Further, amelioration of depressive symptoms by pharmacotherapy h as resulted in augmented NKCA. Serotonin, an indoleamine implicated in the pathophysiology of affective disorders, enhances NKCA in vitro and lymphocy tes possess serotonin transporters and receptors. The present study evaluat ed NKCA in depressed outpatients before and during treatment with the selec tive serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac(R)). Further, t he SSRIs, fluoxetine and paroxetine (Paxil(R)), were also incubated in vitr o with lymphoid cells to evaluate possible direct effects of SSRIs on NKCA. Depressed outpatients were administered fluoxetine (20 mg/day) for 4 weeks . NKCA and severity of depression were evaluated at weeks 0, 1, 2, and 4. S erum concentrations of fluoxetine and norfluoxetine were obtained as well. Mononuclear cells obtained from nonpatient volunteers were incubated with p harmacologic concentrations of fluoxetine or paroxetine and NKCA measured w ith a standard chromium release assay. Fluoxetine treatment resulted in dec reased symptoms of depression and increased serum concentrations of fluoxet ine and norfluoxetine. Further, fluoxetine treatment was associated with au gmented NKCA in a subgroup of depressed outpatients exhibiting low NKCA at baseline. Fluoxetine had no effect on NKCA in depressed individuals exhibit ing high NKCA at baseline. Incubation of mononuclear cells with fluoxetine and paroxetine augmented NKCA in vitro. The enhancing effects of antidepres sants on NKCA in vivo and in vitro indicate a possible direct drug interact ion with lymphoid cells during pharmacotherapy, suggesting that pharmacolog ic treatment of depression may result in enhanced immune competence as inde xed by enhanced NKCA and that NKCA could be pharmacologically augmented wit h antidepressants in individuals with compromised immune function.