内源性白细胞介素-10调节诱导新月体性肾小球肾炎的Th1反应。

Endogenous interleukin-10 regulates Th1 responses that induce crescentic glomerulonephritis.

作者信息

Kitching A R, Tipping P G, Timoshanko J R, Holdsworth S R

机构信息

Center for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Center, Clayton, Victoria, Australia.

出版信息

Kidney Int. 2000 Feb;57(2):518-25. doi: 10.1046/j.1523-1755.2000.00872.x.

DOI:10.1046/j.1523-1755.2000.00872.x

PMID:10652028

Abstract

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 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.

CONCLUSIONS

Endogenous IL-10 counter-regulates nephritogenic Th1 responses and attenuates crescentic GN.

摘要

背景

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。

方法

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。

结果

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。