The Evolving Systemic and Local Biomarker Milieu at Different Stages of Disease Progression in Rat Adjuvant-Induced Arthritis

Abstract

Introduction Rats with adjuvant-induced arthritis (AIA) were necropsied on 14 occasions during preclinical, acute clinical and chronic clinical stages of AIA progression to characterize local (joint protein extracts) and systemic (serum) levels of mediators regulating inflammation and bone erosion in conjunction with lymphoid tissue-specific leukocyte kinetics. Results Systemic increases in alpha1 acid glycoprotein, tumor necrosis factor-α (TNFα), interleukin (IL)-17, transforming growth factor beta (TGFβ), and chemokine (C-C motif) ligand 2 (CCL2) together with local IL-1α/β and TGFβ enrichment and local lymphoid hyperplasia preceded the onset of clinical disease and joint damage. Systemic upregulation of TNFα, IL-6, IL-17, TGFβ, IL-18, CCL2, receptor activator of nuclear factor-κβ ligand (RANKL), and prostaglandin E 2 during acute and/or chronic AIA coincided with systemic leukocytosis and CD4+ T cell increase in blood and spleen. In contrast, progression of joint erosions during clinical AIA was associated with intraarticular increases in IL-1α/β, IL-6, RANKL, IL-17, TGFβ, CCL2, and KC/GRO and also a dramatic decline in osteoprotegerin. Conclusion These data indicate that systemic and local events in inflammatory arthritis are discrete processes, driven by multiple cellular and humoral mediators with distinct kinetic profiles.

Advances in Osteoimmunology: Pathophysiologic Concepts and Treatment Opportunities

“…Like osteoporosis, RA is a very complex pathological condition with a prominent immunopathological component. In respective rodent RA models, such as the adjuvant-induced arthritis and the collagen-induced arthritis models, RA – as in the human disease – coincides with a systemic upregulation of IL-1β, IL-8, CCL2, RANKL, TNF-α, IL-17, and other mediators of inflammation [41,42]. …”

Merlot grape pomace hydroalcoholic extract improves the oxidative and inflammatory states of rats with adjuvant-induced arthritis

“…The disease involves well known immunological events, such as participation of T cells, B cells, macrophages and pro-inflammatory cytokines (Stolina et al, 2009). The progression of the disease is also accompanied by an increased oxidative stress in the lesion sites (Seven, Güzel, Aslan, & Hamuryudan, 2008).…”

Protective Effects of Indomethacin and Cyclophosphamide but Not of Infliximab on Liver Metabolic Changes Caused by Adjuvant-Induced Arthritis

“…However, it is now accepted that a wide spectrum of cellular and humoral elements of the immune system is activated and contributes to disease pathology. The involvement of T cells, autoantibody-producing B cells, and macrophage-like cells has been demonstrated [1][2][3][4][5].…”

“…Pro-inflammatory mediators instigate and perpetuate immune-mediated chronic soft tissue inflammation and eventually joint destruction. Inflammatory mediators can be released in the local compartment, including joint or regional lymph nodes, and systemic compartments (circulation and distant lymphoid tissues) [5,[7][8][9][10][11]. As one or more of these molecules have been shown to play a role in the initiation and/or progression of immunemediated arthritis, therapy targeting T and B cells or inhibitors of inflammatory mediators has been developed to counteract the chronic inflammatory process in RA [12].…”