EXPERIMENTAL SUBSTANTIATION OF THE IMMUNOSTIMULATING EFFECT OF BRANCHED-CHAIN AMINO ACIDS UNDER STRESS

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The immune system, as one of the key integral and regulatory systems of the body, is most sensitive to stress factors that may be due to starvation, emotional, mental and physical overstrain. The need for branched-chain amino acid (BCAA): valine, leucine, isoleucine for the functioning of immune system cells is determined primarily by their participation in protein biosynthesis. The aim is to study the effect of BCAAs on cytokine synthesis in male Wistar rats on the background of cyclic starvation. Materials and methods. A study of 2 months duration was performed on 60 rats, which were divided into 3 groups (20 rats in each group): rats of the control group (K-group) received standardized balanced laboratory feed for rodents ad libitum. The animals of the 1st experimental group (O-1 group) were fed according to the following scheme: the first day - feed ad libitum, the second and the third day - fasting, the rats of the 2nd experimental group (O-2 group) were given feed according to the same scheme, but with the addition of BCAA at a dosage of 70 mg/kg body weight per day. In the serum of rats, cytokine levels were determined: GM-CSF, INF-γ, IL-10, IL-12p70, IL-13, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, TNF-α on the Luminex 200 multiplex analyzer (Luminex Corporation, USA). Statistical processing of the results was performed using the IBM SPSS Statistics Version 20.0 application package (“IBM”, USA). Results and discussion. The results of the study of the effect of BCAA on the cytokine profile of rats under cyclic starvation are presented in Table 1. When assessing changes in the cytokine profile of Th1/Th2, there were no statistically significant differences for most of the studied parameters (Table 1). Changes were found only in the IL-10 level between the experimental and control groups, in the IL-1a level between the control and the O-2 group (BCAA), and in the IL-2 level between the control and the O-1 group. Cyclic starvation (O-1 group) had small effect on the content of IL-10 in the blood serum of animals. Consumption of BCAA in rats contributed to a significant decrease in the level of IL-10 compared with the control and the O-1 group. Fasting also did not significantly affect the level of IL-1a. But the addition of BCAA to the diet caused a statistically significant increase in serum cytokine levels in rats in the O-2 group. Cyclic starvation of rats (O-1 group) resulted in a statistically significant decrease in serum IL-2 levels compared to controls. The addition of BCAA to the diet of animals contributed to an increase at the trend level (p < 0.10) of the value of this indicator compared with the O-1 group in the absence of significant differences with the control. It is well known that the lack of macro- and micronutrients during fasting causes hypotrophy of lymphoid tissue. This means a decrease in the number of circulating lymphocytes, which is a consequence of the inhibition of DNA synthesis and cell proliferation. Humoral and cellular immunity is reduced by reducing the cell population of antibody-producing cells and T-lymphocytes, and the immunoregulatory index CD4+/CD8+ decreases, which indicates the development of immunosuppression [2, 3]. Under fasting conditions, the addition of BCAA to the diet has a certain immunotropic effect due to the effect on the synthesis of proteins, RNA and DNA. BCAAs are involved in the metabolism of almost all cells involved in the regulation of the immune response [1, 6]. Increasing the level of BCAA, the induction of oxidative processes in cells, causes activation of the mTOR signaling pathway and contributes to a decrease in the level of TGF-β, IL-6, and IL-10 [5]. This mechanism may explain the decrease in the level of IL-10 when BCAA is added to the ration of rats compared with the control and the group of rats that did not receive a mixture of amino acids. Against this background, the activation of signaling pathways contributes to the switching of the Th2 immune response to the predominant production of Th1 cytokines and the suppression of Treg cells [4, 6]. The result is an increase in the level of IL-1a and the restoration of the content of IL-2 in the O-2 group of animals. Conclusion. The consumption of BCAA by rats for 2 months on the background of cyclic starvation causes a decrease in the level of IL-10 and an increase in serum levels of IL-1a and IL-2 due to the activation of signaling pathways that regulate switching of the Th2 immune response to the predominant production of Th1 cytokines.

About the authors

E N Trushina

Federal Research Centre of Nutrition, Biotechnology and Food Safety, Moscow

A N Timonin

Federal Research Centre of Nutrition, Biotechnology and Food Safety, Moscow

N A Ryger

Federal Research Centre of Nutrition, Biotechnology and Food Safety, Moscow

O K Mustafina

Federal Research Centre of Nutrition, Biotechnology and Food Safety, Moscow

V D Kuznetsov

First Moscow State Medical University named after I.M. Sechenov, Moscow

References

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