The International Journal of Neuropsychopharmacology

Special Section

Effects of antidepressants on the production of cytokines

Gunter Kenis a1c1 and Michael Maes a1
a1 Department of Psychiatry and Neuropsychology, University of Maastricht, Maastricht, The Netherlands


There is now evidence that major depression is associated with an up-regulation of the inflammatory response system (IRS). One of the major factors in this IRS activation is the hyperproduction of pro-inflammatory cytokines. Recently, a number of studies examined whether there is a causative role of these inflammatory mediators in the aetiology of major depression. Studies with animal models and cytokine immune therapy in humans suggest that pro-inflammatory cytokines induce depressive symptomatology. Moreover, these depressive symptoms can be effectively reversed by antidepressant treatment. Thus, it may be suggested that antidepressants suppress pro-inflammatory cytokine production and/or action, resulting in improvement of depressive symptoms. The influence of antidepressants on cytokine production has been examined in culture systems in vitro, and in animal models of depression – in which cytokine production is induced by endotoxin administration. Results suggest that antidepressants of several classes decrease the production of pro-inflammatory cytokines such as interferon-γ and tumour necrosis factor-α, and increase that of interleukin-10, an anti-inflammatory cytokine. Further, the effect of antidepressive treatment on cytokine secretion and on plasma levels of cytokines in depressed patients has been studied. Unfortunately, different approaches to examine cytokine production and different techniques to measure cytokines in plasma are used in these studies. Despite this, current data indicate a normalization of cytokine plasma levels and cytokine production after antidepressant treatment. It is clear, however, that more research is warranted and we strongly argue the need for higher standardization in the methodology used to examine the cytokine network in depressed patients.

(Received January 28 2002)
(Reviewed April 22 2002)
(Revised June 3 2002)
(Accepted June 5 2002)

Key Words: Antidepressant; cytokine; immune system; interleukin; major depression.

c1 Address for correspondence: G. Kenis, University of Maastricht, Department of Psychiatry and Neuropsychology, Pb 616 (UNS 50, box 38), 6200 MD Maastricht, The Netherlands. Tel.: +31-43-3884108 Fax: +31-43-3671096 E-mail: