Participation of serotoninergic system in neuroimmunomodulation: intraimmune mechanisms and the pathways providing an inhibitory effect.

Exogenous serotonin administration as well as its precursor 5-oxytryptophan, blockade of the ferment inactivation by MAO inhibition, impairment of the monoamine binding, in other words, all the ways of elevation of active serotonin level, result in the inhibition of the immune response. On the contrary, exclusion of the serotoninergic system by the nuclei raphe lesion and the blockade of the synthesis ferments by p-chlorphenylalanine and p-chloramphetamine stimulates it. The present analysis permits us to conclude that the nuclei raphe serotoninergic system provides an inhibitory mechanism of the immune response modulation, that is realized via the hypothalamus-hypophysis-adrenals axis. Immune response modulation by the extraimmune control system is possible only be means of the mechanisms that are present in the immunocompetent system. Investigation of the cellular basis of physiological mechanisms of serotoninergic regulation of the immune process made it possible to determine alterations in the correlation of functionally different cell populations in animals with elevated serotonin level. An inhibitory action which serotonin produces upon the immunogenesis, is based on the attenuation of suppressor cell function, an earlier than under the normal immune response development emergence of suppressor in the population of cell organs, and their longer presence, that is to some extent connected with the redistribution of cell populations in the immunocompetent organs. After serotonin administration only the antigen-nonspecific immunosuppression is activated. In evolutionary terms the mechanisms of nonspecific suppression have been formed earlier than those of specific ones (Calkins & Stutman, 1978; Mijawaki, Seki, Kubo & Tanigushi, 1979). It is quite reasonable that extraimmune modulation, and psychoneuroimmunomodulation by monoamine systems in particular, can be performed by means of this ancient antigen-nonspecific mechanism of the immune response regulation. In this case, the modulation of immunological reactivity should correspond to these endogenous and environmental influences. Thus, activation of the nonspecific suppression induced through the serotoninergic system can be considered as the universal mechanism which on the one hand completes control of the immune homeostasis and on the other may be the precondition of the development of pathological states caused by the reduction of immunological status.