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Immune cells are dysfunctional during long-term ethanol consumption and may contribute to the progression from healthy to problem drinking. Lymphocytes from mice with chronic ethanol exposure characterized by impaired functional activity, manifested in the combination of increased spontaneous proliferation against the background of low sensitivity to T- cell mitogens.
Objectives
We first demonstrated that original compound meta-chloro-benzhydryl-urea (m-ch-BHU) in vitro restored long-term alcoholized mice lymphocytes activity through GABA(A) receptors. We also revealed the possibility of animal’s behavioral regulation by the transplantation of immune cells with definite functional characteristics, also modulated by psychoactive drugs. Based on the previous results we investigated effects of m-ch-BHU modulated lymphocytes transplantation in recipients with experimental alcoholism.
Methods
Male (CBAxC57Bl/6)F1 mice with 6-month 10% ethanol exposure were undergoing the transplantation of syngeneic long-term alcoholized mice lymphocytes, pretreated in vitro with m-ch-BHU. Recipient’s ethanol consumption, nervous and immune systems functional activities were estimated.
Results
It was shown that transplantation of lymphocytes with in vitro m-ch-BHU modulated functional activity caused in syngeneic recipients with chronic alcohol exposure essential ethanol consumption decrease and stimulation of motor and exploratory activities in the “open field” against the background of cytokines modulation in brain. The significant stimulation of humoral immune response, estimated by the relative number of antibody-forming spleen cells, and stimulation of DTH reaction were also detected in recipients after lymphocytes transplantation.
Conclusions
Results demonstrated that transplantation of m-ch-BHU modulated lymphocytes caused positive psychoneuroimmunomodulating effect in animals with chronic alcohol exposure, so, it may be considered as a promising method in the treatment of alcoholism
Cell technologies actively used in the treatment of many diseases. These technologies are based on manipulating the patient’s cells outside the body, as a result of which cells acquire a higher therapeutic potential.
Objectives
No doubt the essential role of immune cells and their biologically active products in the pathogenesis of depression, which allows to view the modulated immune cells as model objects for developing new approaches to immunotherapy for depression.
Methods
(CBAxC57Bl/6) F1 depressive-like male mice, developed under the long-term social stress, were undergoing the transplantation of syngeneic immune cells with in vitro caffeine-modulated functional activity. Recipient’s behavior, immune and nervous systems functional activity were studied.
Results
It was found that immune cells isolated from depressive-like mice and treated in vitro with caffeine change their properties and after intravenous administration to syngeneic depressive-like recipients have a significant positive psycho- and neuroimmunomodulatory effects, affecting the main depression pathogenetic mechanisms: behavioral editing (reduction of anhedonia, stimulation of exploratory behavior and activity in the forced swimming test); hippocampal neurogenesis stimulation against the background of increased BDNF; modulation of cytokine production by brain cells, indicating a decrease in neuroinflammation; modulation of the immune system functional activity (stimulation of the immune response, splenocytes proliferation, reducing systemic inflammation, decrease spleen tryptophan catabolism).
Conclusions
The results serve as an experimental substantiation of a fundamentally new approach to immunotherapy of depression based on the introduction of immune cells with functional activity modulated outside the body and open up the possibility of developing new methods of immunotherapy of depressive states in humans.
Disclosure
No significant relationships.
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