A Complete Freund’s Adjuvant-Induced Murine Model as an Experimental Platform to Explore Systemic Inflammation in Rheumatoid Arthritis

Introduction: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that compromises joint integrity and triggers extra-articular manifestations associated with oxidative distress and systemic inflammation. This study analysed the onset of inflammation in the CFA-induced arthritis model by characterising peripheral molecular and tissue changes to elucidate the systemic inflammatory mechanisms. Methods: For this purpose, 16 male Wistar rats (12 weeks) were divided into two groups; the ART received intradermal and intra-articular CFA, while the CTL received saline solution; the oedema/arthritic index was monitored during the experiment. Synovial fluid, plasma, lymph nodes, rectus femoris muscle, and peritoneal lavage were analysed. Results: Principal component analysis revealed a difference between CTL and ART in multiple compartments. In the lymph node, Dimension 1 (89.38%) associated the ART group with greater oxidative damage (LPO, H₂O₂, O₂⁻, NO, PCO) and increased activity of SOD, CAT, and NP-SH, with lower levels of GPx. In muscle, Dimension 1 (78.11%) linked the ART group to increased TNF-α, IL-1β, Mfn1, Hsp70, and Nrf2, while Dimension 2 reflected an atrophic axis influenced by increased myostatin. In plasma, Dimension 1 (88.97%) associated the ART with increased activity of CAT, SOD, LPO, and RS, indicating oxidative distress with an adaptive antioxidant response. In peritoneal macrophages, Dimension 1 (86.92%) indicated increased activity (number, adhesion, phagocytosis, lysosomal volume, RS). Conclusion: It is concluded that CFA induces a multifactorial systemic inflammatory state, integrated with redox imbalance and mitochondrial dysregulation, approaching the extra-articular phenotypes of RA found in human patients, providing a basis for pathophysiological studies and targeted interventions.