The role of the metabolic status of lymphocytes in the pathogenesis of rheumatoid arthritis

Abstract

Objective: to study in dynamics metabolic changes in lymphocytes on the model of adjuvant-induced rheumatoid arthritis (RA) in warm-blooded animals.Material and methods. The RA model was elicited by administering Freund's complete adjuvant (AF) to male Wistar rats. Lymphocyte metabolism was corrected with a mixture of citric and succinic acids, which was injected for 4 weeks (at doses of 17 and 88 mg/kg body weight) from the first day of model formation. Animals of the control group were injected subcutaneously with isotonic sodium chloride solution. The total number of leukocytes, the size of lymphocytes and the activity of lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) in these cells were determined. Changes in the musculoskeletal system were assessed radiographically and actometrically in the «open field» model.Results and discussion. In the first 2 weeks of the experiment in the model group, an increase in the level of leukocytes by 65% compared to the control (p=0.002) was noted, an increase in the activity of lymphocytes SDH by 51% and a decrease in the total («horizontal») mobility of animals by 30% were also revealed. Subsequently, the level of leukocytes decreased by 25%, the activity of LDH and SDH – by 38%, the radius of lymphocytes – by 14% (p<0.01). The action of carboxylic acids was dose-dependent: at the maximum dose, no statistically significant differences in the total number of leukocytes, LDH and SDH activity in lymphocytes, as well as their sizes were found between the group with adjuvant- induced RA and the control group.Conclusion. In animals with adjuvant-induced RA, correction of the metabolic status of lymphocytes with a mixture of citric and succinic acids, which are key substrates of the Krebs cycle, led to a decrease in structural damage of musculoskeletal system and, as a consequence, to the maintenance of normal range of motion.

Keywords

• inflammatory process
• physical activity
• lactate dehydrogenase
• citric acid
• lymphocyte metabolism
• rheumatoid arthritis
• subchondral sclerosis
• succinate dehydrogenase
• energotropic effect
• succinic acid