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 cell proliferation during rat anti-Thy-1 nephritis by blocking its action with IL- 1 receptor antagonist (IL-1ra). Anti-Thy-1 nephritis was induced by intravenous injection of 5 mg/kg OX-7 IgG (day 0) into inbred Wistar rats. Groups of animals (n = 9) were implanted with a micro-osmotic pump on day - 1, which delivered 25 μg hour human recombinant IL-1ra or saline continuously until the rats were killed at day 6, the peak of mesangial cell proliferation. Immunostaining showed that IL-1 was expressed by mesangial cells during disease. IL-1ra treatment did not affect the mild, but significant, proteinuria seen after OX-7 injection. Compared with saline treatment, IL-1ra treatment reduced mesangial cell proliferation (↓ 249%; P < 0.05), glomerular hypercellularity (↓ 29%; P < 0.05), and glomerular macrophage accumulation (↓ 20%; P < 0.05). However, IL-1ra treatment had no effect on glomerular IL-1 β mRNA expression and caused only a small reduction in the high levels of glomerular expression of platelet-derived growth factor-β protein (↓ 6%; P < 0.05). IL-1ra caused a modest reduction in the marked up-regulation of glomerular transforming growth factor-β1 mRNA expression on day 6 (↓ 26%; P < 0.05), although urinary, excretion of this factor was unaffected. Interestingly, IL-1ra treatment had relatively little effect upon glomerular deposition of laminin, fibronectin, and collagen type IV seen in this acute disease. In conclusion, this study has 1) demonstrated that IL-1 is expressed by mesangial cells in vivo, 2) demonstrated that IL-1 is a mesangial cell growth factor in experimental mesangioproliferative nephritis, and 3) suggests that IL-1 has little or no fibrogenic activity in mesangial matrix deposition.