Interleukin-10 (IL-10) has been recognized as a
growth factor for rat mesangial cells in vitro; however, its role in mesangioproliferative
glomerulonephritis is unknown. We studied the expression of
IL-10 mRNA in the rat
anti-Thy-1 model of mesangioproliferative
glomerulonephritis (experiment 1) and, subsequently, the effects of blocking
IL-10 during
anti-Thy-1 nephritis using the
IL-10 inhibitor,
AS101 (experiment 2). In experiment 1, PCR analysis failed to detect
IL-10 mRNA in normal rat kidney, however, a clear signal for
IL-10 mRNA was evident on day 6 of
anti-Thy-1 nephritis. In situ hybridization showed
IL-10 mRNA expression in focal glomerular areas in
anti-Thy-1 nephritis. Combined in situ hybridization and immunohistochemistry showed that glomerular
IL-10 mRNA was expressed by both macrophages and mesangial cells. In experiment 2, treatment with
AS101 significantly downregulated renal
IL-10 gene expression, as demonstrated by semiquantitative PCR. However, the induction of glomerular hypercellularity, mesangial proliferation (PCNA+ cells), mesangial cell activation (alpha-SMA expression) and macrophage accumulation (ED1+ cells) seen in saline-treated
anti-Thy-1 nephritis was unaffected by
AS101 treatment. In conclusion, renal
IL-10 gene expression is upregulated during pathological mesangial cell proliferation in rats with
anti-Thy-1 nephritis. However, the inability of
IL-10 suppression with
AS101 to prevent
anti-Thy-1 disease suggests that
IL-10 is not essential for pathological mesangial cell proliferation.