ESTABLISHED MURINE LUPUS NEPHRITIS DOES NOT RESPOND TO EXOGENOUS INTERLEUKIN-1 RECEPTOR ANTAGONIST - A ROLE FOR THE ENDOGENOUS MOLECULE

Interleukin 1 beta (IL-1 beta) is a potent inflammatory cytokine and I L-1 beta gene expression is elevated in the kidneys of mice with lupus nephritis. This study was designed to examine whether pharmacological administration of the IL-I receptor antagonist (IL-1ra) would reduce the inflammation in MRL 1pr/1pr mice with lupus nephritis. Human recom binant IL-1ra (RA) or saline (SA) was infused by intraperitoneal osmot ic minipumps in 16 week old mice (n = 9, group RA or n = 12, group SA, respectively). Age matched MRL + / + mice served as normal controls. At the end of 4 weeks of treatment glomerular filtration rates (5.4 +/ - 0.4 vs 5.6 +/- 0.4 ml/min/kg BW), proteinuria (6.0 +/- 1.0 vs 5.5 +/ - 1.2 mu g IgC/day) glomerular volumes (571 +/- 30 vs 509 +/- 25 mu m( 3) X 10(3)), mesangial volumes (172 +/- 23 vs 158 +/- 17 mu m(3) X 10( 3)), and cells/glomerulus (519 +/- 51 vs 506 +/- 47) were not signific antly different between RA and SA groups respectively. There was also no significant differences in spleen sizes, plasma IgG and anti-dsDNA antibody levels despite achieving levels of IL-1ra of over 0.8 mu g/ml in RA mice. Circulating IL-1 was not detected by bioassay in the plas ma of diseased or normal mice. In fact, diseased, saline treated mouse plasma inhibited the cell proliferation assay in the presence of IL-1 , and dilution studies showed that the endogenous inhibitors were of h igh titre. Although IL-1 may play a role in the renal injury of lupus nephritis, pharmacological inhibition with IL-1ra in animals with esta blished injury is without effect. Evidence would suggest that endogeno us inhibitors already provide sufficient protection against IL-1 media ted inflammation.