Immunomodulatory properties of caffeine and caffeine-treated immune cells in depression-like state
Authors: Markova E. V. , Knyazheva M. A. 
Published: June 2023

Depression is one of the leading global health problems worldwide. A significant increase in prevalence among the working-age population, as well as high comorbidity, partial or complete drug resistance in a third of patients determines the need to develop new approaches to the treatment of depression. Violation of mutual regulation of the main homeostatic systems plays an important role in the pathogenesis of depression. Psycho- and immunopathology are closely interrelated: pathological changes in the functioning of both systems occur simultaneously and are interdependent. This determines the prospects for the treatment of depression based on immunological approaches. Caffeine, a drug known for its psychoneuromodulatory properties, is an adenosine receptor antagonist with a pronounced dose-dependent effect. Adenosine receptors are expressed by both CNS cells and cells of the immune system, which determines its immunomodulatory properties. The similarity of both phenotypes and functions of the cellular elements of the immune and nervous systems, as well as the unidirectional effect of most psychoactive drugs on the central nervous system and the immune system, determines the interest in studying the immunomodulatory properties of caffeine for a targeted effect on the functional activity of immune cells, with a view to their subsequent use as model objects for the normalization of neuroimmune regulatory connections disturbed in a depressive state. Previously, we first demonstrated the possibility of editing depression-like behavior by immune cells precultivated with caffeine and showed the central mechanisms of this effect aimed at stimulating neuroplasticity processes and reducing neuroinflammation. The aim of this study was to evaluate the functional phenotype of immune cells in depressive-like animals after in vitro treatment of cells with caffeine, as well as the effects of transplantation of caffeine-precultured immune cells on the parameters of the functional activity of the immune system of syngeneic depressive-like recipients. As a result of the study, it was shown that low concentrations of caffeine increase the spontaneous and mitogen-induced proliferative activity of splenocytes of depression-like male mice (CBA x C57BL/6)F1 in vitro; this changes the spontaneous and mitogen-stimulated production of cytokines TNFa IL-1b, IFNg, IL-2, and IL-10 by these cells. After intravenous administration of the precultured with caffeine depression-like donor’s splenocytes to syngeneic depression-like recipients, stimulation of the humoral immune response was observed in the latter, assessed by an increase in both the relative and absolute number of antibody-forming spleen cells. Stimulation of spontaneous proliferative activity of lymphocytes in splenocyte culture was also registered. The data obtained indicate a positive effect of caffeine in vitro on the immune cell’s functional activity, as well as a positive immunomodulatory effect of the immune cells precultured with caffeine in a depression-like state in vivo.