IMMUNE CELLS AS A POTENTIAL THERAPEUTIC AGENT IN THE TREATMENT OF DEPRESSION

Abstract

The immune and neuroendocrine systems play a critical role in maintaining a dynamic homeostasis in normal conditions and at mental maladaptation. Psycho- and immunopathology closely interrelated: pathological changes in the functioning of both systems occur simultaneously and are interdependent. Depression, as a mental disorder, is a major public health concern. The estimations are showing rise of the depression’s incidence in the future. However, currently used therapy of depression doesn’t provide a complete cure. It is known that a violation of neuroimmune interaction is an essential link in the pathogenesis of the disease, having a negative impact on its course, making the clinical picture worse, reducing effectiveness of the therapy, therefore, it’s urgent to search for a new treatment approaches. There are a sufficient amount data on the immune cells and their biologically active products leading role in the pathogenesis of depression. The unidirectional effect of most psychoactive substances on the central nervous system and the immune system confirms intersystem mutual regulation and allows considering the immune cells as model objects for influencing the intersystem functional relationship; so, cells immunotherapy can be the method of choice in the treatment of depressive disorders. We first demonstrated the possibility of animal’s behavior directed regulation by the transplantation of immune cells with definite functional characteristics, including those with functional activity modulated extracorporeally by a psychoactive substance. Based on the previous results we investigated the effect of the in vitro caffeine- treated immune cells on the behavior and immune phenotypes in depressive-like singeneic recipients. Transplantation of caffeine-treated splenocytes from depressive-like donors has been shown to induce depressive-like behavior editing in syngeneic recipients, which was manifested in anhedonia decrease, stimulation of exploratory behavior in the Open Field test and motor activity in the Porsolt forced swimming test. Recipient’s behavioral changes were registered on the background of decreased brain pro- inflammatory cytokines (TNFα, IL-1β, IL-6, IFNγ) and IL-10 increased in some pathogenetically significant for depressive-like state brain structures (hippocampus, hypothalamus, frontal cortex, striatum), which indicates a decrease in neuroinflammation. It was also detected recipient’s immune system functional activity modulation. The cytokines-mediated mechanisms of depressive-like behavior editing by the in vitro caffeine- modulated immune cells are discussed.