Negative Immunoregulatory Effects of Antidepressants: Inhibition of Interferon-γ and Stimulation of Interleukin-10 Secretion

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 20; no. 4; pp. 370 - 379
• Main Authors: Maes, Michael, Song, Cai, Lin, Ai-Hua, Bonaccorso, Stefania, Kenis, Gunter, De Jongh, Raf, Bosmans, Eugene, Scharpé, Simon
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.1999; Nature Publishing
• Subjects: Adult; Antidepressants; Antidepressive Agents, Second-Generation - adverse effects; Antidepressive Agents, Tricyclic - adverse effects; Antiviral Agents - antagonists & inhibitors; Biological and medical sciences; Clomipramine - adverse effects; Cytokines; Depression; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interferon-gamma - antagonists & inhibitors; Interferon-γ; Interleukin-10; Interleukin-10 - metabolism; Male; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Recombinant Proteins; Serotonin Uptake Inhibitors - adverse effects; Sertraline - adverse effects; Trazodone - adverse effects; Depression; Cytokines; Interleukin-10; Interferon-γ; Antidepressants; Human; Healthy subject; Serotonin; Psychotropic; Cytokine; Trazodone; Clomipramine; Tricyclic compound; Reuptake inhibitor; In vitro; Sertraline; Biological activity; Immunomodulator; Interleukin 10; Antidepressant agent; Gamma interferon
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1016/S0893-133X(98)00088-8

There is now some evidence that major depression is accompanied by activation of the inflammatory response system. There is also some evidence that antidepressants may suppress the release of cytokines, such as interleukin-1β (IL-1β) and IL-6 by activated monocytes and IL-2 and interferon-γ (IFNγ) by activated T cells. This study was carried out to examine the effects of clomipramine, sertraline, and trazodone on the stimulated production of IFNγ, a pro-inflammatory cytokine, and IL-10, a negative immunoregulatory cytokine. Whole blood of nine healthy volunteers was stimulated with PHA, 5 μg/mL and LPS, 25 μg/mL for 72 hr with and without incubation with clomipramine, 10−6 and 10−9 M, sertraline, 10−6 and 10−8 M, and trazodone, 10−6 and 10−8 M. All three antidepressants significantly reduced IFNγ secretion, whereas clomipramine and sertraline significantly increased IL-10 secretion in culture supernatant. All three antidepressants significantly reduced the IFNγ/IL-10 ratio. The results suggest that antidepressants, at concentrations in the therapeutical range, have negative immunoregulatory effects through inhibition of IFNγ and stimulation of IL-10 release.