Kinetics of knee synovial lavage inflammation in rodent models of collagen induced arthritis. (171.15)

Abstract

Abstract Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation, swelling, and destruction of joints. In this study we used intra-articular lavage of the knee joint to easily and rapidly assess the kinetics of cellular infiltration and cytokine production within the local joint synovial environment during disease in rodent models of arthritis. In collagen induced arthritis in rats, knees of arthritic animals had increased cellularity composed of neutrophils, monocytes and T cells as well as marked increases in pro-inflammatory cytokines and chemokines including IL-1b, IL-6, and KC. The kinetics of infiltration showed an initial infiltration of monocytes shortly followed by a significant increase in neutrophil infiltration that strongly correlated with paw swelling. CD4+ T cells increased as well, but were not found in high numbers in the joint until after maximal paw swelling had been reached. We also found that the influx of monocytes into the knee joint space correlated with increased levels of KC, IL-1b, and IL-6, with KC levels preceding the subsequent neutrophil influx. Mouse models show similar disease course in regards to both inflammation and cytokine production in the synovial knee lavage. Understanding the kinetics of disease in the local joint presents new opportunities for biomarker development, target identification, and improvement of mechanistic understanding of disease processes in rodent models of arthritis.