Blackwell Publishing Journal Backfiles 1879-2005
Background Mice with constitutive transgenic (tg) expression of interleukin-4 (IL-4) develop autoimmune-type disorders resembling lupus nephritis. The kidneys show progressive glomerulosclerosis with immunoglobulin (Ig) and complement deposition.Methods This study investigated the role of renal IL-4 expression and the relevance of glomerular Ig deposition in the pathogenesis of glomerulosclerosis in IL-4tg mice. The mice were treated with either IL-4 neutralizing antibody or the glucocorticoid methylprednisolone (MP). To further clarify whether the renal lesions were exclusively immune-mediated, IL-4tg mice were cross-bred with δ chain deficient mice (δ MT-/-), which are unable to produce Igs.Results Glomeruli of anti-IL-4-treated tg mice showed a normal structure with negligible Ig deposits. Similarly, in MP-treated tg mice only trace amounts of glomerular Ig deposits could be detected, although in comparison with wt mice, increased mesangial collagen deposition was evident. Despite complete absence of renal Ig deposits, IL-4tg/δMT-/- mice developed progressive glomerulosclerosis with mesangial accumulation of collagen types I, IV and V. Renal IL-4 expression was observed in both anti-IL-4- and MP-treated IL-4 tg mice, as well as in IL-4tg/δMT-/- mice. There was no statistically significant difference in the number of glomerular T cells and macrophages between the groups.Conclusions Our data demonstrate that in this model glomerulosclerosis developed independently of and prior to Ig deposition, and imply that the initial accumulation of glomerular extracellular matrix was due to renal IL-4 expression.
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