Serotonin and its precursors as modulators of the immunological responsiveness in mice.

Central nervous system regulation of endocrine functions is mediated by neurotransmitters, via hypothalamic hypophysiotropic factors which in turn control anterior pituitary functions. The evidence of serotonergic-endocrine interrelations with regard to adrenal, thyroid, gonadal and prolactin functions is fast accumulating. Our study extends the importance of those interrelations to some functions of the immune system. Multiple administration of 5-hydroxytryptamine(serotonin) or its precursor, 5-hydroxy-L-tryptophan(5-HTPH), produces marked depression of T cell dependent, humoral, hemolytic, primary immune response in mice. L-tryptophan, a more distant serotonin precursor, produces slight but significant depression of this immune response. Multiple treatment of mice infected with Friend Leukemia Virus (FLV) with serotonin or 5-HTPH alone or in combination with cyclophosphamide (Cytoxan) results in significant delay of the clinical progression of the infection. L-tryptophan produces a modest but significant improvement. Administration of serotonin or 5-HTPH causes a marked reduction of the thymus weight. It is reasonable to postulate that the described effects result from the thymus involution which affects the T cell compartment of the immune system. This is the consequence of hormonal imbalance caused by the alteration of the serotonin biosynthetic pathway in the brain. The adrenal cortex is not implicated in the mediation of this effect. Since many clinically used drugs affect the serotonin metabolism, the clinical consequences of the resulting alteration of the immunological responsiveness should be considered.