Effect of interleukin-10 treatment on crescentic glomerulonephritis in rats

Research output: Contribution to journalArticleResearchpeer-review

32 Citations (Scopus)

Abstract

This study examined the utility of interleukin-10 (IL-10), a cytokine with potent anti-macrophage and anti-Th1 activity, in the treatment of experimental anti-glomerular basement membrane (GBM) nephritis in the rat. Accelerated anti-GBM disease was induced in Sprague-Dawley rats by immunization with rabbit IgG, followed five days later by an i.v. injection of anti-GBM serum. Groups of four rats received daily s.c. injections of recombinant mouse IL-10 (500, 10 or 0.2 μg/kg/day) or saline (control) from the time of anti-GBM serum administration until being killed on day 14. IL-10 treatment suppressed the skin DTH response as measured by skin thickness (44 to 62% ↓ vs. control, P < 0.05). Compared to saline controls, IL-10 treatment had no beneficial effect on renal function, proteinuria of histological damage (including crescent formation) at any dose examined. A detailed analysis of high dose IL-10 (500 μg/kg/day) and saline treated animals was undertaken. Saline controls had marked glomerular macrophage accumulation and proliferation, which was augmented by IL-10 treatment (46 to 99% ↑ and 44 to 143% ↑, respectively; P < 0.05). Immunohistochemical staining found no difference in the state of macrophage activation between the groups, as determined by the percentage of macrophages expressing IL-1β protein. Northern blot analysis of whole kidney RNA demonstrated an 830% increase in IL-1β mRNA expression in saline controls compared to normal rat kidney. High dose IL-10 treatment reduced IL-1β mRNA levels by 60% compared to controls (P < 0.05), but did not significantly reduce glomerular IL-1β protein expression. IL-10 treatment increased serum levels of rat anti-rabbit IgG, induced a rat anti-mouse IL-10 response and augmented glomerular deposition of rat C3. In conclusion, IL-10 was not an effective treatment for rat crescentic anti-GBM glomerulonephritis. This may have been due to the failure of IL-10 to achieve a sufficient reduction in IL-1β expression and macrophage participation in disease, or promotion of the Th2 immune response.

Original languageEnglish
Pages (from-to)1809-1817
Number of pages9
JournalKidney International
Volume51
Issue number6
DOIs
Publication statusPublished - 1 Jan 1997
Externally publishedYes

Cite this