Inflammatory polyarthritis induced by mercuric chloride in the Brown Norway rat

BACKGROUND : Mercuric chloride (HgCl 2 ) 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 IFNγ and in vivo up-regulation of IL-4 suggest that HgCl 2 -induced autoimmunity occurs in a Th2 lymphokine environment. EXPERIMENTAL DESIGN : HgCl 2 -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 HgCl 2 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-α/β 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 HgCl 2 , and FACS was used to assess the number of peripheral blood OX1 9 + 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 : HgCl 2 induces a T cell-dependent inflammatory arthritis in the BN rat. In contrast with other animal models, HgCl 2 -induced arthritis is associated with an apparent Th2 lymphokine response.