Professor and Chair Midwestern Univ., Downers Grove, United States
Disclosure(s):
Michael Volin, PhD: No financial relationships to disclose
Introduction/Rationale: 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.
