Negative immunoregulatory effects of antidepressants: Inhibition of interferon-gamma and stimulation of interleukin-10 secretion

There is now some evidence that major depression is accompanied by activati on of the inflammatory response system. There is also some evidence that an tidepressants may suppress the release of cytokines, such as interleukin-1 beta (IL-2 beta) and IL-6 by activated monocytes and IL-2 and interferon-ga mma (IFN gamma) by activated T cells. This study was carried out to examine the effects of clomipramine, sertraline, and trazodone on the stimulated p roduction of IFN gamma, a pro-inflammatory cytokine, and IL-10, a negative immunoregulatory cytokine. Whole blood of nine healthy volunteers was stimu lated with PHA, 5 mu g/mL and LPS, 25 mu g/mL for 72 hr with and without in cubation 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 anti-depressants signi ficantly reduced IFN gamma secretion, whereas clomipramine and sertraline s ignificantly increased IL-10 secretion in culture supernatant. All three an tidepressants significantly reduced the IFN gamma/IL-10 ratio. The results suggest that antidepressants, at concentrations in the therapeutical range, have negative immunoregulatory effects through inhibition of IFN gamma and stimulation of IL-10 release. [Neuropsychopharmacology 20:370-379, 1999] ( C) 1999 American College of Neuropsychology. Published by Elsevier Science Inc.