Effect of neutralizing antibodies to IL-10 and C5 on the renal damage caused by a pathogenic human anti-dsDNA antibody

Objectives. There is considerable evidence suggesting that anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibodies are involved in the pathogenesis of lupus nephritis. It was shown previously using severe combined immune deficient (SCID) mice that when the hybridomas secreting human immunoglobulin G (IgG) anti-dsDNA antibodies, RH14 and DIL-6, were implanted intraperitoneally the antibodies produced by RH14, but not DIL-6, deposited in the kidneys, caused pathological changes in the renal tissues and induced proteinuria. In this study we have further analysed the effect of activated terminal complement proteins and interleukin-10 (IL-10) in the pathogenesis of glomerulonephritis caused by the RH-14. Methods. SCID mice implanted with RH-14 or DIL-6 cell lines were treated with neutralizing antibodies to IL-10 (mAb B-S10) or anti-complement factor 5 (anti-C5) (mAb BB5.1) intraperitoneally. Control groups received either an isotype control antibody (135.8) or phosphate-buffered saline (PBS). Serum human IgG levels and proteinuria were estimated and the extent of renal involvement was examined by histopathological and electron microscopic techniques. Results. While there was a tendency to reduce proteinuria in the anti-IL-10 injected group the anti-C5 injected group showed a significant reduction in proteinuria (P