Glomerulonephritis is an important cause of renal failure thought to be caused by autoimmune damage to the kidney. While each type of glomerulonephritis begins with a unique initiating stimulus, subsequent common inflammatory and fibrotic events lead to a final pathway of progressive renal damage. In this article the different forms of inflammatory glomerulonephritis and their diagnosis are discussed. In a review of therapy both immediate life saving treatment given when glomerulonephritis causes acute renal failure and more specific treatments designed to modify the underlying mechanisms of renal injury are considered.
Administration of mercuric chloride (HgCl(2)) to Brown Norway rats causes Th2-dominated autoimmunity with raised immunoglobulin E concentrations and gut vasculitis, both of which are T-cell dependent, peak at 14 days after starting HgCl(2) and then spontaneously resolve. If animals are re-challenged with HgCl(2) 6 weeks after initial exposure, they are resistant to autoimmunity, developing only attenuated disease. Recently, a separate phase of early caecal vasculitis was described beginning 24 h after initiating HgCl(2) and prior to caecal entry of T cells. Previous work suggested this early vasculitis was alpha beta T-cell independent and implied a role for mast cells. We further tested this hypothesis by performing a histological study during the first 93 h following HgCl(2) challenge defining the precise relationship between gut mast cell degranulation and appearing caecal vasculitis. We also studied whether early caecal vasculitis enters a resistant phase upon re-challenge with HgCl(2). We show a direct correlation between mast cell degranulation and early caecal vasculitis following initial HgCl(2) challenge. We demonstrate resistance to re-challenge in this phase of injury, with results at re-challenge also showing a correlation between mast cell degranulation and early caecal injury.
SUMMARYAdministration 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 autoimmunity 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 (onetenth 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.
SummaryAdministration of mercuric chloride (HgCl 2 ) to Brown Norway rats causes Th2 dominated autoimmunity including a caecal vasculitis. Disease peaks 14 days after starting HgCl 2 after which animals immunoregulate spontaneously. In a third phase, if animals are rechallenged with HgCl 2 6 weeks later they appear resistant, developing only attenuated disease. Previous studies suggested a role for CD8
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