You are on page 1of 7

The Pathophysiology of

Rheumatoid Arthritis

Annu Rev Immunol. et al. RA Is Characterised by Synovitis and Joint Destruction NORMAL RA Inflamed Synovial synovial membrane membrane Major cell types: • T lymphocytes • macrophages Pannus Cartilage Minor cell types: • fibroblasts • plasma cells • endothelium • dendritic cells Synovial Major cell type: Capsule fluid • neutrophils Cartilage thinning Adapted from Feldmann M. . 1996.14:397-440.

30(suppl 2):1-6. etc IL-1 Soluble factors T cell and direct cell–cell contact Antigen- presenting Macrophage cells B cell or macrophage IL-1 and Synoviocytes TNF- Chondrocytes Pannus Articular Production of collagenase and cartilage other neutral proteases Arend W. 2001. Semin Arthritis Rheum. TNF-. .Numerous Cellular Interactions Drive the RA Process Rheumatoid Immune complexes B cell factors Bacterial products IL-1.

Ca. USA: Amgen Inc.1b Capsule Synovial space C h o n d ro c y te s Pannus Osteoblasts Osteoclasts B one PGE2 = prostaglandin-E2 Dinarello C. 3rd ed. . Thousand Oaks. 2001. Proinflammatory and Anti-inflammatory Cytokines in Rheumatoid Arthritis: A Primer for Clinicians. Moldawer L..IL-1b and TNF-: Proinflammatory Cytokines in the Rheumatoid Joint High endothelial venule Bone O s t e o b l a s ts O s t e o c l a s ts Synovial IL-8 C a r t il a g e PGE2 membrane IL-6 N e u t r o p h i ls T N F - I L .

NO = nitric oxide . PGE2 = prostaglandin-E2.IL-1 and TNF- Have a Number of Overlapping Proinflammatory Effects Proinflammatory Proinflammatory effects of IL-1 effects of TNF- COX-2 TNF- PGE2 Osteoclast NO IL-1 activation Adhesion molecules cell death Angiogenic Chemokines factors Collagenases IL-6 COX-2 = cyclo-oxygenase type 2.

IL-1 Plays a Pivotal Role in the Inflammatory and Destructive Processes of RA IL-1 Activates monocytes/ Induces fibroblast Activates Activates macrophages proliferation chondrocytes osteoclasts Inflammation Synovial pannus Cartilage Bone formation breakdown resorption .

**P <0. Clin Exp Rheumatol. et al.06.003 vs patients with erosions Fong K.12:55-58. 1994.Patients With Erosive RA Have Higher Levels of IL-1 Than Patients Without Erosions Mean Cytokine Concentrations in Synovial Fluid 700 700 600 600 TNF- (pg/mL) IL-1 (pg/mL) 500 500 400 400 300 300 ** * 200 200 100 100 0 Patients Patients Non-RA 0 Patients Patients Non-RA With Erosions Without Erosions Patients With Erosions Without Erosions Patients (n = 8) (n = 20) (n = 10) (n = 8) (n = 20) (n = 10) *P <0. .