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

Depressive illness has been associated with variations of several aspects of immune functioning, as well as alterations of cytokine production in stimulated lymphocytes. In the present investigation we sought to determine whether pharmacologically-induced reductions of mood in healthy, male subjects would be associated with alterations in the levels of circulating IL-1β or IL-6 or to in vitro lymphocyte proliferation in response to T cell mitogens, PHA and Con A. Lowering tryptophan levels by means of a tryptophan-deficient amino acid mixture, which reduced plasma tryptophan and serotonin (5-HT) levels, produced a lowering of mood in a subset of male subjects (that had no personal or family history of depression) relative to subjects that received a balanced amino acid mixture. Correlational analyses revealed that the change of mood (particularly depression and anger) in subjects that received the tryptophan-free mixture was related to the extent of the tryptophan or 5-HT reductions. However, while fenfluramine administration resulted in recovery of tryptophan and 5- HT levels, this was not accompanied by recovery of mood. Furthermore, it was observed that the lowering of tryptophan levels and the reduced mood were not accompanied by variations of the cytokine levels or cell proliferation. Evidently, transient and modest alterations of 5-HT or mood induced by a tryptophan-free amino acid mixture were insufficient to promote variations of immune activity or circulating IL-1β or IL-6 levels. Even if depression were related to immune disturbances, 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.