Influence of acute tryptophan depletion on mood and immune measures in healthy males

Depressive illness has been associated with variations of several aspects o f immune functioning, as well as alterations of cytokine production in stim ulated lymphocytes. In the present investigation we sought to determine whe ther pharmacologically-induced reductions of mood in healthy, male subjects would be associated with alterations in the levels of circulating IL-1 bet a or IL-6 or to in vitro lymphocyte proliferation in response to T cell mit ogens, PHA and Con A. Lowering tryptophan levels by means of a tryptophan-d eficient amino acid mixture, which reduced plasma tryptophan and serotonin (5-HT) levels, produced a lowering of mood in a subset of male subjects (th at had no personal or family history of depression) relative to subjects th at received a balanced amino acid mixture. Correlational analyses revealed that the change of mood (particularly depression and anger) in subjects tha t received the tryptophan-free mixture was related to the extent of the try ptophan or 5-HT reductions. However, while fenfluramine administration resu lted in recovery of tryptophan and 5-HT levels, this was not accompanied by recovery of mood. Furthermore, it was observed that the lowering of trypto phan levels and the reduced mood were not accompanied by variations of the cytokine levels or cell proliferation. Evidently, transient and modest alte rations of 5-HT or mood induced by a tryptophan-free amino acid mixture wer e insufficient to promote variations of immune activity or circulating IL-1 beta or IL-6 levels. Even if depression were related to immune disturbance s, the mood and 5-HT alterations associated with this type of manipulation may be too brief to promote immune changes comparable with those ordinarily associated with severe or chronic depressive illness. (C) 1998 Elsevier Sc ience Ltd. All rights reserved.