ROLE OF INTERLEUKIN-1 IN MESANGIAL CELL-PROLIFERATION AND MATRIX DEPOSITION IN EXPERIMENTAL MESANGIOPROLIFERATIVE NEPHRITIS

We examined the functional role of interleukin (IL)-1 in mesangial cel l proliferation during rat anti-Thy-1 nephritis by blocking its action with IL-1 receptor antagonist (IL-1ra). Anti-Thy-1 nephritis was indu ced by intravenous injection of 5 mg/kg OX-7 IgG (day 0) into inbred W istar rats. Groups of animals (n = 9) were implanted with a micro-osom otic pump on day -1, which delivered 25 mu g/hour human recombinant IL -1ra or saline continuously until the rats were killed at day 6, the p eak of mesangial cell proliferation. Immunostaining showed that IL-1 w as expressed by mesangial cells during disease. IL-1ra treatment did n ot affect the mild, but significant, protein-uria seen after OX-7 inje ction. Compared with saline treatment, IL-1ra treatment reduced mesang ial cell proliferation (down arrow 24%; P < 0.05), glomerular hypercel lularity (down arrow 29%; P < 0.05), and glomerular macrophage accumul ation (down arrow 20%; P < 0.05). However, IL-1ra treatment had no eff ect on glomerular IL-1 beta mRNA expression and caused only a small re duction in the high levels of glomerular expression of platelet-derive d growth factor-beta protein (down arrow 6%; P < 0.05). IL-1ra caused a modest reduction in the marked up-regulation of glomerular transform ing growth factor-beta 1 mRNA expression on day 6 (down arrow 26%; P < 0.05), although urinary excretion of this factor was unaffected. Inte restingly, IL-1ra treatment had relatively little effect upon glomerul ar deposition of laminin, fibronectin, and collagen type IV seen in th is acute disease. In conclusion, this study has 1) demonstrated that I L-1 is expressed by mesangial cells in vivo, 2) demonstrated that IL-1 is a mesangial cell growth factor in experimental mesangioproliferati ve nephritis, and 3) suggests that IL-1 has little or no fibrogenic ac tivity in mesangial matrix deposition.