Anti-Inflammatory effects of antidepressants through suppression of the interferon-gamma/interleukin-10 production ratio.
There is some evidence that major depression--in particular, treatment-resistant depression (TRD)--is accompanied by activation of the inflammatory response system and that proinflammatory cytokines may play a role in the etiology of depression. This study was carried out to examine the effects of antidepressive agents, i.e., imipramine, venlafaxine, L-5-hydroxytryptophan, and fluoxetine on the production of interferon-gamma (IFN-gamma), a proinflammatory cytokine, and interleukin-10 (IL-10), a negative immunoregulatory cytokine. Diluted whole blood of fluoxetine-treated patients with TRD (mean age, 50.6+/-3.9 years) and age-matched healthy controls (mean age, 51.6+/-1.7 years) and younger healthy volunteers (mean age, 35.4+/-9.6 years) was stimulated with phytohemagglutinin (1 microg/mL) and lipopolysaccharide (5 microg/mL) for 48 hours with and without incubation with the antidepressants at 10-6 M and 10(-5) M. IFN-gamma and IL-10 were quantified by means of enzyme-linked immunoassays. The ratio of IFN-gamma to IL-10 production by immunocytes was computed because this ratio is of critical importance in determining the capacity of immunocytes to activate or inhibit monocytic and T-lymphocytic functions. All four antidepressive drugs significantly increased the production of IL-10. Fluoxetine significantly decreased the production of IFN-gamma. All four antidepressants significantly reduced the IFN-gamma/IL-10 ratio. There were no significant differences in the antidepressant-induced changes in IFN-gamma or IL-10 between younger and older healthy volunteers and TRD patients. Tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin-noradrenaline reuptake inhibitors, as well as the immediate precursor of serotonin, have a common, negative immunoregulatory effect by suppressing the IFN-gamma/IL-10 production ratio. It is suggested that the therapeutic efficacy of antidepressants may be related to their negative immunoregulatory effects.
Clinical Research Center for Mental Health, Antwerp, Belgium.
M
M
Kubera
A H
AH
Lin
G
G
Kenis
E
E
Bosmans
D
D
van Bockstaele
M
M
Maes
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000328:Adult; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003511:Cyclohexanols / Q000494:pharmacology; D003866:Depressive Disorder / Q000097:blood* / Q000188:drug therapy; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D006801:Humans; D007099:Imipramine / Q000494:pharmacology; D007371:Interferon-gamma / Q000097:blood / Q000187:drug effects*; D016753:Interleukin-10 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D000069470:Venlafaxine Hydrochloride
D000928:Antidepressive Agents; D003511:Cyclohexanols; D005473:Fluoxetine; D016753:Interleukin-10; D000069470:Venlafaxine Hydrochloride; D007371:Interferon-gamma; D006916:5-Hydroxytryptophan; D007099:Imipramine