Psychoneuroimmunomodulating effect of lymphocytes with ortho-fluoro-benzonal modulated activity in syngeneic long-term alcoholized recipients

TL;DR

A compound called ortho-fluoro-benzonal can improve immune and behavioral functions in mice with long-term alcohol exposure when used to modulate lymphocytes before transplantation.

Contribution

The study introduces a novel approach using ortho-fluoro-benzonal-modulated lymphocytes for treating alcoholism through adoptive immunotherapy.

Findings

ortho-fluoro-benzonal modulated lymphocytes reduced ethanol consumption in alcoholized mice.

The treatment stimulated behavioral activity and altered cytokine levels in key brain regions.

Transplanted lymphocytes enhanced humoral immune response and were found in the spleen and brain of recipients.

Abstract

Lymphocytes are dysfunctional during long-term ethanol consumption and may contribute the progression from healthy to problem drinking. GABAA receptors are molecular targets of ethanol on lymphocytes, potentiating the effects of alcohol.

We first demonstrated that original compound ortho-fluoro-benzonal, artificial GABA receptor ligand, has immunostimulating properties and is able to restored long-term alcoholized mice lymphocytes activity in vitro through GABAA receptors.  Based on the previous results we investigated effects of the ex vivo ortho-fluoro-benzonal modulated lymphocytes in recipients with experimental alcoholism.

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 ortho-fluoro-benzonal. Recipient’s ethanol consumption, parameters of the nervous and immune systems functional activities were estimated.

It was shown that lymphocytes modulated ex vivo with ortho-fluoro-benzonal after intravenous injection caused in syngeneic long-term alcoholized recipients ethanol consumption decrease and stimulation of behavioral activity in the “open field” test against the background of changes in the level of a number of cytokines in pathogenetically significant brain structures. Stimulation of humoral immune response, estimated by the relative number of antibody-forming spleen cells was also detected in recipients after lymphocytes transplantation. The injected immune cells were recorded in the parenchyma of the spleen and brain of recipients, which suggests, in particular, their direct influence on these functions.

Results demonstrated that transplantation of ortho-fluoro-benzonal-modulated lymphocytes caused positive psychoneuroimmunomodulating effect in long-term alcoholized recipients, which makes it possible to consider adoptive immunotherapy as a promising method in the treatment of alcoholism.

None Declared