INFLAMMATORY POLYARTHRITIS INDUCED BY MERCURIC-CHLORIDE IN THE BROWN-NORWAY RAT

BACKGROUND: Mercuric chloride (HgCl2) induces an autoimmune syndrome i n 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 inj ury, including glomerulonephropathy and necrotizing vasculitis of the gut. The high total IgE levels and evidence showing ex vivo down-regul ation of IFN gamma and in vivo up-regulation of IL-4 suggest that HgCl 2-induced autoimmunity occurs in a Th2 lymphokine environment. EXPERIM ENTAL DESIGN: HgCl2-autoimmunity was induced in BN rats using standard methods. Anti-collagen (types I and II) Ab and IgG subclasses were me asured by ELISA. Arthritis was scored on Days 13 to 17 after HgCl2 tre atment. Ankle joints and synovium were examined with standard histolog ic and immunohistochemical techniques. The incidence and severity of a rthritis were compared in normal and R73 (anti-alpha/beta T cell recep tor mAb)-treated BN rats. After R73 treatment, T cell function was ass essed by measuring the total IgE and anti-type II collagen response to HgCl2, and FAGS was used to assess the number of peripheral blood OX1 9(+) lymphocytes (T cell marker). RESULTS: A self-limiting inflammator y arthritis develops in more than 82% of animals and is more severe in males. Histologically, there is a predominant ED1(+) macrophage synov ial infiltrate, areas of fibrinoid necrosis, and vasculitis and erosio ns 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 arthr itis. CONCLUSIONS: HgCl2 induces a T cell-dependent inflammatory arthr itis in the BN rat. In contrast with other animal models, HgCl2-induce d arthritis is associated with an apparent Th2 lymphokine response.