Kitching A R, Tipping P G, Timoshanko J R, Holdsworth S R
Center for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Center, Clayton, Victoria, Australia.
Kidney Int. 2000 Feb;57(2):518-25. doi: 10.1046/j.1523-1755.2000.00872.x.
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.
GN was initiated in sensitized mice by the intravenous administration of sheep antimouse glomerular basement membrane globulin. Renal injury was evaluated 21 days later.
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 micromol/L; IL-10 +/+, 23 +/- 1 micromol/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-gamma production by cultured splenocytes was increased (IL-10-/- 7.9 +/- 2. 5 ng/4 x 106 cells, IL-10+/+ 0.28 +/- 0.09 ng/4 x 106 cells, P < 0. 05), but IL-4 production was unchanged.
Endogenous IL-10 counter-regulates nephritogenic Th1 responses and attenuates crescentic GN.
白细胞介素（IL）-10在调节免疫反应的Th1/Th2优势方面起关键作用。外源性给予IL-10可抑制致肾炎性Th1反应，抑制巨噬细胞功能，并减轻新月体性肾小球肾炎（GN）。为确定内源性IL-10的作用，我们比较了IL-10缺陷（IL-10-/-）和正常（IL-10+/+）C57BL/6小鼠中致肾炎性免疫反应和新月体性GN的发展情况。
通过静脉注射羊抗小鼠肾小球基底膜球蛋白在致敏小鼠中引发GN。21天后评估肾损伤情况。
给予抗肾小球基底膜球蛋白后，正常（IL-10+/+）C57BL/6小鼠发生增殖性GN，偶见新月体形成，肾小球CD4+ T细胞和巨噬细胞积聚，以及纤维蛋白沉积。采用相同的诱导方案，IL-10-/-小鼠发生更严重的GN。新月体形成（IL-10-/-, 占肾小球的23±2%；IL-10+/+, 占5±2%）、肾小球CD4+ T细胞[IL-10-/-, 每个肾小球横截面积（c/gcs）1.0±0.2个细胞；IL-10+/+, 0.3±0.05 c/gcs]、肾小球巨噬细胞（IL-10-/-, 4.8±0.3 c/gcs；IL-10+/+, 1.7±0.2 c/gcs）、纤维蛋白沉积[纤维蛋白评分（范围0至3+）；IL-10-/-, 1.10±0.04；IL-10+/+, 0.6±0.07]以及血清肌酐（IL-10-/-, 30±2 μmol/L；IL-10+/+, 23±1 μmol/L）在IL-10-/-小鼠中均显著增加（P<0.05）。对致肾炎性抗原（羊球蛋白）的循环抗体（IL-10-/-, 1.05±0.16 OD单位；IL-10+/+, 0.63±0.08 OD单位）和皮肤迟发型超敏反应（皮肤肿胀；IL-10-/-, 0.21±0.03 mm；IL-10+/+, 0.12±0.02 mm）也增加（均P<0.05）。培养的脾细胞产生的干扰素-γ增加（IL-10-/- 7.9±2.5 ng/4×106细胞，IL-10+/+ 0.28±0.09 ng/4×106细胞，P<0.05），但IL-4产生未改变。
内源性IL-10对致肾炎性Th1反应起反向调节作用，并减轻新月体性GN。
