P D Kiely1, S Thiru, D B Oliveira. 1. Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, United Kingdom.
Abstract
BACKGROUND: Mercuric chloride (HgCl2) induces an autoimmune syndrome in susceptible strains of rodent. In the Brown Norway (BN) rat, this is characterized by autoreactive T cells, high levels of total IgE, IgG autoantibodies, including anti-collagen types I and II, and tissue injury, including glomerulonephropathy and necrotizing vasculitis of the gut. The high total IgE levels and evidence showing ex vivo down-regulation of IFN gamma and in vivo up-regulation of IL-4 suggest that HgCl2-induced autoimmunity occurs in a Th2 lymphokine environment. EXPERIMENTAL DESIGN: HgCl2-autoimmunity was induced in BN rats using standard methods. Anti-collagen (types I and II) Ab and IgG subclasses were measured by ELISA. Arthritis was scored on Days 13 to 17 after HgCl2 treatment. Ankle joints and synovium were examined with standard histologic and immunohistochemical techniques. The incidence and severity of arthritis were compared in normal and R73 (anti-alpha/beta T cell receptor mAb)-treated BN rats. After R73 treatment, T cell function was assessed by measuring the total IgE and anti-type II collagen response to HgCl2, and FACS was used to assess the number of peripheral blood OX19+ lymphocytes (T cell marker). RESULTS: A self-limiting inflammatory arthritis develops in more than 82% of animals and is more severe in males. Histologically, there is a predominant ED1+ macrophage synovial infiltrate, areas of fibrinoid necrosis, and vasculitis and erosions of cartilage. The peak anti-collagen (type I and II) Ab titer does not correlate with arthritis incidence or severity. Treatment with R73 markedly reduces the rise in total IgE and IgG anti-type II collagen, reduces OX19+ peripheral blood lymphocytes, and abolishes the arthritis. CONCLUSIONS: HgCl2 induces a T cell-dependent inflammatory arthritis in the BN rat. In contrast with other animal models, HgCl2-induced arthritis is associated with an apparent Th2 lymphokine response.
BACKGROUND:Mercuric chloride (HgCl2) induces an autoimmune syndrome in susceptible strains of rodent. In the Brown Norway (BN) rat, this is characterized by autoreactive T cells, high levels of total IgE, IgG autoantibodies, including anti-collagen types I and II, and tissue injury, including glomerulonephropathy and necrotizing vasculitis of the gut. The high total IgE levels and evidence showing ex vivo down-regulation of IFN gamma and in vivo up-regulation of IL-4 suggest that HgCl2-induced autoimmunity occurs in a Th2 lymphokine environment. EXPERIMENTAL DESIGN:HgCl2-autoimmunity was induced in BN rats using standard methods. Anti-collagen (types I and II) Ab and IgG subclasses were measured by ELISA. Arthritis was scored on Days 13 to 17 after HgCl2 treatment. Ankle joints and synovium were examined with standard histologic and immunohistochemical techniques. The incidence and severity of arthritis were compared in normal and R73 (anti-alpha/beta T cell receptor mAb)-treated BN rats. After R73 treatment, T cell function was assessed by measuring the total IgE and anti-type II collagen response to HgCl2, and FACS was used to assess the number of peripheral blood OX19+ lymphocytes (T cell marker). RESULTS: A self-limiting inflammatory arthritis develops in more than 82% of animals and is more severe in males. Histologically, there is a predominant ED1+ macrophage synovial infiltrate, areas of fibrinoid necrosis, and vasculitis and erosions of cartilage. The peak anti-collagen (type I and II) Ab titer does not correlate with arthritis incidence or severity. Treatment with R73 markedly reduces the rise in total IgE and IgG anti-type II collagen, reduces OX19+ peripheral blood lymphocytes, and abolishes the arthritis. CONCLUSIONS:HgCl2 induces a T cell-dependent inflammatory arthritis in the BN rat. In contrast with other animal models, HgCl2-induced arthritis is associated with an apparent Th2 lymphokine response.