Cytokine changes following methotrexate treatment in rat adjuvant-induced arthritis 2257725

Abstract

Abstract Introduction Rheumatoid arthritis (RA) is a chronic autoimmune disease that results in joint inflammation leading to systemic bone and cartilage destruction. The most common first-line treatment for RA is the disease-modifying antirheumatic drug methotrexate (MTX). MTX is though to work in RA by suppressing the autoimmune response by regulating leukocyte activity and protecting joint tissues. Rat adjuvant-induced arthritis (AIA) is a rodent model that mimics the pathogenesis of human RA. In this study, we will investigate the effects of MTX on cytokine expression in rat AIA joint and spleen tissues. Methods Rat AIA studies were performed, where MTX was administered preventatively 3 times before the onset of arthritis symptoms (day 9). Rat ankle joints and spleens were harvested from AIA rats. Tissue samples were homogenized, and protein extracts from MTX-treated animals and control AIA rats were assessed for 36 different cytokines using a cytokine array. Cytokines with altered expression in MTX-treated animals were quantified using specific ELISAs. Results Animals that received MTX treatment did not develop arthritis as determined by articular index scoring and joint circumference measurements, compared to control animals. MTX-treated AIA animals showed significant decreases in ankle MCP-1, ICAM-1, and CINC-1 levels and spleens from these animals had significantly reduced CINC-1 levels. Conclusion The reduced levels of CINC-1 and MCP-1 in joint tissues of MTX-treated animals could result in reduced neutrophil and monocyte recruitment, resulting in the reduced joint inflammation. Additionally, the reduction of ICAM-1 could be responsible for the reduced migration of immune cells into the MTX treated joints. Finally, the reduction of acute phase reactants, including CINC-1, in the spleen may be responsible for the reduction in systemic inflammation seen with MTX treatment. Further studies could focus on other cytokines and signaling pathways to develop a better understanding of the mechanism of action of MTX. Funding Source n/a Topic Categories Therapeutic Approaches to Autoimmunity (THER)