Assistant Professor Arizona State University, United States
Introduction:: Rheumatoid arthritis (RA) associated inflammation leads to an imbalance in healthy tissue homeostasis. Homeostatic imbalance in the affected tissue joints exacerbates inflammation. Therefore, restoring homeostasis is necessary for the remission of rheumatoid arthritis. Modulation of energy pathways in immune cells is shown to reduce symptoms of RA in Collagen Induced Arthritis (CIA) mice. However, the role of these modulators in restoring homeostasis remains to be investigated. Here-in, the efficacy of the vaccine - paKG(PFK15+bc2) to restore homeostasis in different stages of RA namely, early, intermediate and late-stage were examined.
Materials and Methods:: Splenocytes and cells from paw tissues were obtained from vaccine-treated, no treatment and naïve mice on days 28, 42 and 70 corresponding to early, intermediate and late-stage RA respectively. Using Real-time flux assay, the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of the paw and spleen were determined to assess glycolysis and mitochondrial respiration.
Results, Conclusions, and Discussions:: The ECAR and OCR measurements showed a significant difference between the vaccine-treated and no treatment mice. In all three stages of the disease, the glycolysis and mitochondrial respiration was significantly reduced in the treatment group as compared to the no treatment. In addition, the treatment group in all stages exhibited glycolysis and maximum respiration similar to naïve mice thus indicating the restoration of homeostasis. Therefore, this study shows the metabolic modulator-paKG(PFK15+bc2) is able to restore homeostasis significantly in early, intermediate and late stages of RA in CIA mice.
