The effect of repeated amitriptyline and desipramine administration on cytokine release in C57BL/6 mice

This study examines the effects of repeated amitriptyline and desipramine a dministration (10 mg/kg. IF) on the immunoreactivity of saline-injected C57 BL/6 mice, as evaluated by the ability of splenocytes to reduce a tetrazoli um salt to formazan (MTT test), to proliferate, and to produce cytokines, s uch as interleukin (IL)-1, IL-2, IL-4, IL-6, IL-10 and interferon gamma (IF N-gamma). Desipramine and amitriptyline administered for one or two weeks e nhance the biochemical (estimated by MTT test) and proliferative activities of splenocytes. One and two weeks administration of desipramine significan tly reduces the secretion of IL-4 an antiinflammatory cytokine, Amitriptyli ne administration for four weeks stimulates the proliferative activity of s plenocytes and enhances IL-2 bioactivity, whereas four weeks desipramine am inistration does not change these parameters in comparison to saline treate d control mice. Prolonged desipramine administration (seven and 28 days) si gnificantly increased the bioactivity of IL-l. I;our weeks of prolonged adm inistration of amitriptyline and desipramine induces a significant increase in the secretion of IL-IO, a cytokine with immunosuppressive and anti-infl ammatory activities. The results show that the immunoregulatory effects of tricyclic antidepressants in C57BL/6 mice depend on the drugs used and on t he duration of administration. (C) 2000 Elsevier Science Ltd. All rights re served.