[Experimental approach to the treatment of lupus nephritis by use of an accelerated model of the NZBxNZW mouse disease (author's transl)]. / Approche expérimentale du traitement des glomérulonéphrites lupiques à l'aide d'un modèle accéléré de la maladie des souris NZBxNZW.

An accelerated model of the NZBxNZW mouse disease is described. The acceleration of the disease was induced by the simultaneous injections of DNA complexed to methylated bovine serum albumin and of bacterial lipopolysaccharide which allow for the production, early in life, of high levels of anti-DNA antibodies. This new model was found to be suitable for therapeutic studies in mice with accelerated disease treated with cyclophosphamide and heparin.

[Hypothesis: immune complex glomerulonephritis and auto-immunity (author's transl)]. / Glomérulonéphrite à complexes immuns et auto-immunité.

Experimental studies on the NZBxNZW mouse lupus disease and on the development of immune complex (IC) glomerulonephritis in mouse infected with Escherichia coli lead us to state the following hypothesis: two types of factors are implicated in the development of immune complex glomerulonephritis: 1) specific factors leading to the production of IC involving antigens from the triggering agents; 2) non specific factors leading to the production of IC involving auto-antigens.

Immune complex glomerulonephritis in mice infected with Escherichia coli.

C57Bl/6 mice were injected intraperitoneally with 10(8) to 2 x 10(8) living K 38 Escherichia coli (E. coli) and serological changes and kidney involvement were studied. E. coli were found in the blood 45 min to 24 hr after injection. In serum, large amounts of deoxyribonucleic acid (DNA) were present 24 hr after E. coli injection, and thereafter disappeared. Seven days after infection, antibodies directed against E. coli, anti-DNA antibodies and C1q-binding substances were found in serum and the kinetics of the variations of these parameters were studied until day 35. Kidney lesions were evaluated immunochemically and by optical and electron microscopy. In the glomeruli, heavy granular deposits of IgG and IgM were constantly found in mesangium and along capillary walls. In most kidneys slight granular deposits of IgG and IgM were also found in the tubules. Histological studies revealed in the glomeruli mild endocapillary cell proliferation, focal thickening of glomerular basement membrane and dense deposits in mesangial and subendothelial areas and inside the glomerular basement membrane; in the tubules dense deposits were focally observed inside the tubular basement membrane.

Sequential study of C 1 q-binding substances and of anti-DNA antibodies in (NZB X NZW)F1 mice: evidence for an acute phase of the lupus disease in 2-month-old mice.

Longitudinal studies of C 1 q and DNA-binding substances were performed in sera from 38 (NZB X NZW)F1 female mice between days 39 and 150 of life. Results suggest a two-phase evolution of circulating immune complexes and anti-DNA antibodies in young (NZB X NZW)F1 mice and show the existence of an acute phase of the disease during the second month of life of these mice.