We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Endogenous interleukin-10 regulates Th1 responses that induce crescentic glomerulonephritis.
- Authors
Kitching, A. Richard; Tipping, Peter G.; Timoshanko, Jennifer R.; Holdsworth, Stephen R.
- Abstract
Endogenous interleukin-10 regulates Th1 responses that induce crescentic glomerulonephritis. Background. Interleukin (IL)-10 plays a pivotal role in regulating the Th1/Th2 predominance of immune responses. Exogenously administered IL-10 suppresses nephritogenic Th1 responses, inhibits macrophage function, and attenuates crescentic glomerulonephritis (GN). To determine the role of endogenous IL-10, the development of the nephritogenic immune response and crescentic GN was compared in IL-10–deficient (IL-10-/-) and normal (IL-10+/+) C57BL/6 mice. Methods. GN was initiated in sensitized mice by the intravenous administration of sheep antimouse glomerular basement membrane globulin. Renal injury was evaluated 21 days later. Results. Following the administration of anti-glomerular basement membrane globulin, normal (IL-10+/+) C57BL/6 mice developed proliferative GN with occasional crescents, glomerular CD4+ T-cell and macrophage accumulation, and fibrin deposition. Using an identical induction protocol, IL-10-/-mice developed more severe GN. Crescent formation (IL-10-/-, 23 ± 2% of glomeruli; IL-10+/+ , 5 ± 2%), glomerular CD4+ T cells [IL-10-/-, 1.0 ± 0.2 cells per glomerular cross-section (c/gcs); IL-10 +/+, 0.3 ± 0.05 c/gcs], glomerular macrophages (IL-10-/-, 4.8 ± 0.3 c/gcs; IL-10 +/+ , 1.7 ± 0.2 c/gcs), fibrin deposition [fibrin score (range 0 to 3+); IL-10-/-, 1.10 ± 0.04; IL-10+/+ , 0.6 ± 0.07], and serum creatinine (IL-10-/-, 30 ± 2 μmol/L; IL-10 +/+ , 23 ± 1 μmol/L) were all significantly increased in IL-10-/- mice (P < 0.05). Circulating antibody (IL-10-/-, 1.05 ± 0.16 OD units; IL-10+/+ , 0.63 ± 0.08 OD units) and cutaneous delayed-type hypersensitivity (skin swelling; IL-10-/-, 0.21 ± 0.03 mm; IL-10+/+ , 0.12 ± 0.02 mm) to the nephritogenic antigen (sheep globulin) were also increased (both P < 0.05). Interferon-γ production by cultured splenocytes was increased...
- Subjects
INTERLEUKIN-10; IMMUNOREGULATION; TH1 cells; TH2 cells
- Publication
Kidney International, 2000, Vol 57, Issue 2, p518
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2000.00872.x