Diffuse Glomerulonephritis Produced in Rabbits by Massive Injections of Bovine Serum Gamma Globulin

Abstract

In the present study, interest was directed toward three aspects of experimental acute diffuse glomerulitis. In the first place, an experimental technique was sought which would produce pathological changes morphologically analogous to those of human giomerulonephritis. In the choice of a method the main objective was to employ one which would give a high incidence of well developed lesions. It was also desired to use a technique as uncomplicated as possible, in order that the relation between lesions and treatment might be more easily perceived and assessed. Secondly, it seemed important to examine, in an experiment wherein neither renal substance nor antirenal serum was used, the possible r61e of antikidney antibodies (autoantibodies) in the development of experimental acute diffuse glomerulitis. The third point in this investigation was concerned with the possibility that changes in blood coagulability might play a r61e in the development of diffuse glomerulitis. This report is accordingly divided into three parts, dealing with each of these aspects separately.

Autoimmune Disease in NZB/Bl Mice

“…The immunological aspects of human and experimental glomenflonephritis have been under investigation for many decades and reviewed elsewhere (14,33,34,44,51,37). Glomerulonephritis has been experimentally induced by hypersensitivity (36,46,17,40,16,12) and autoimmunity (22,48) and occurs also as a sequela of a viral disease (31). Our studies, extending those of Helyer and Howie (18,19), Holmes and Burnet (24), and Aarous (1) have shown that focal and diffuse membranous and chronic lobular glomerulonephritis, with remarkable similarity to a spectrmn of human nephrotic renal diseases, occur spontaneously in NZB/B1 mice and that autoantibodies with antikidney specificities are localized in the glomerular lesions and demonstrable in the serum.…”

Cardiac Lesions Produced in Rabbits by Massive Injections of Bovine Serum Gamma Globulin

“…The use of purified serum gamma globulin by us and of this and other purified antigens by Hawn and Janeway does not support this concept. In our animals intravenous injection of purified bovine serum gamma globulin gave rise to a glomerulonephritis (7) and in almost equal incidence, a granulomatous inflammation of heart valves and valve rings. Also produced, though in a much smaller number of animals, was an arteritis.…”

“…The most important etiological factor in producing lesions in anaphylactically sensitized rabbits is widely considered to be the hypersensitive state. That hypersensitivity existed in our tested animals is indicated by the presence of a positive Arthus reaction and precipitins in the blood (7). However, the coexistence of hypersensitivity and tissue lesions does not, by itself, necessarily demonstrate a pathogenetic relationship between the two.…”

The Effects of Various Horse Serum Fractions in Producing Cardiovascular and Renal Lesions in Rabbits

“…Several factors may have contributed to this decreased intensity of glomerular inflammation. More and Waugh (21) and also Hawn and Janeway (11) gave their animals considerably larger injections of gamma globulin, and employed beef globulin instead of horse globulin. Furthermore, these observers noted the most marked lesions about a week after the initial injection of gamma globulin.…”

“…The third difference between these results and those of previous investigators was the frequency and type of lesion seen after the injection of the gamma globulin fraction (fraction II). Hawn and ~aneway (11) and more recently More and Waugh (21) have reported striking glomerular lesions in the majority of rabbits following somewhat larger single injections of pure bovine gamma globulin. In our experiments, in which 2 injections of less pure equine gamma globulin were employed, the diffuse glomerular lesions seen 1 week after the second injection were present in only 3 of 8 rabbits and were quite mild.…”