Administration of
mercuric chloride to Brown Norway rats results in T helper type 2 (Th2)- dominated autoimmunity characterized by high
immunoglobulin E (
IgE) concentrations, the production of multiple
IgG autoantibodies, including those to glomerular basement membrane (GBM),
arthritis and caecal
vasculitis. After 14 days animals immunoregulate and auto-immunity resolves even if
mercuric chloride injections are continued. In a third phase, if animals are re-challenged with
mercuric chloride 6 weeks later, they show only attenuated autoimmunity with lower
anti-GBM antibody concentrations and
arthritis scores. Resistance to the induction of
anti-GBM antibodies can also be achieved following an initial challenge with low-dose (one-tenth standard dose)
mercuric chloride. We have now studied this resistant phase in more detail. We have shown, first, that following an initial full-dose
mercuric chloride challenge, resistance also affects susceptibility to caecal
vasculitis. Second, following an initial full-dose
mercuric chloride challenge, the
IgE response upon re-challenge is initially accelerated but subsequently enters a resistant phase and third, following an initial challenge with low-dose
mercuric chloride, resistance is also seen to the induction of caecal
vasculitis but is not seen in
IgE serology (where results suggest competing effector and regulatory cell populations). Studying such regulatory phases in animal models of autoimmunity may be of benefit in the future in designing new
therapies for human
vasculitis.