The in vitro immunosuppressive effects of moclobemide in healthy volunteers

Background: Many studies have demonstrated that major depression is related to an activation of the inflammatory response system (IRS) with an increas ed production of proinflammatory cytokines. It has been shown that tricycli c antidepressants and serotonin reuptake inhibitors suppress the activation of the IRS in depression and have negative immunoregulatory effects in vit ro. Little is known on the immune effects of moclobemide, a reversible mono amine oxidase A inhibitor. Methods: We examined, in nine normal volunteers, the in vitro effects of moclobemide on the production of interleukin-6 (IL -6), IL-8, tumor necrosis factor-alpha (TNF alpha), interferon-gamma (IFN g amma), IL-10 and the IL-1 receptor antagonist (IL-1RA) by diluted whole blo od stimulated or not with lipopolysaccharide (LPS)+ phytohemagglutinin (PHA ). Results: Moclobemide 10(-3) and 10(-5) M significantly suppressed the un stimulated production of TNF alpha and IL-8, and significantly enhanced the stimulated-production of IL-10. The production of IL-6, IL-1RA and IFN gam ma was not significantly affected either in the unstimulated or stimulated conditions. Conclusions: Moclobemide has negative immunoregulatory capaciti es through inhibition of the production of proinflammatory cytokines, i.e. TNF alpha and IL-8, and through enhancement of the production of IL-10, an anti-inflammatory cytokine. (C) 2000 Elsevier Science B.V. All rights reser ved.