Argument for the
Classical Concept:
The Active Heymann Nephritis Model
(Autologous Immune
Complex Nephritis)
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If a rat is immunized with certain extracts of its own kidney a severe glomerulonephritis develops. Immune complex formation inside the glomeruli leads to severe proteinuria and eventually renal failure (Heymann et al 1959, Heymann et al 1962). This is a strong argument that an immunological reaction inside the glomeruli is the cause of glomerulonephritis.
Counter-Argument
To develop serious glomerulonephritis in this animal model it is necessary to mix the injected tissue extract with Freund´s adjuvant. This substance is a mixture of mycobacteria emulsified with mannide monooleate in hydrocarbon oils and has been used in countless animal experiments to enhance the immunological reactions. It is a striking fact, however, that in experimental glomerulonephritis no serious kidney damage is produced without the use of Freund´s adjuvant. In the section Experimental Anti-GBM Nephritis I shall show that the reason why Freund's adjuvant produces glomerulonephritis is not an enhancement of the immunological reactions but a toxic effect on the kidneys.
What also has been ignored is that an injection of Freund's adjuvant alone produces typical glomerulonephritis with deposition of immune complexes in the glomeruli (Miettinen 1982, Ravnskov 1989). This means that experimental glomerulonephritis produced with the aid of Freund's adjuvant cannot be used as support of the classical concept, because who knows if it is the immunization, or the injection of the nephrotoxic substance, Freund's adjuvant. or a combination of these measures, that are producing the disease?
The similarity with acute poststreptococcal glomerulonephritis is striking: a streptococcal infection without exposure to toxic chemicals may be harmless (Ravnskov 1978) just as an immunization of the rat without the use of Freund´s adjuvant is harmless. The similarity goes further, because just as an injection of Freund´s adjuvant can produce glomerulonephritis by itself, hydrocarbon exposure alone can do it also. This has most convincingly been demonstrated by the animal experiments.
However, even if Freund´s adjuvant alone can produce glomerulonephritis, the disease becomes more serious if the injection is combined with an immunization. Obviously the immune system is participating in the production of glomerulonephritis, but it is not causing it by itself.