Louis H, Le Moine O, Peny M O, Gulbis B, Nisol F, Goldman M, Devière J
Laboratory of Experimental Immunology, Department of Gastroenterology and Hepatopancreatology, Universite Libre de Bruxelles, Brussels, Belgium.
Gastroenterology. 1997 Mar;112(3):935-42. doi: 10.1053/gast.1997.v112.pm9041256.
BACKGROUND & AIMS: Interleukin (IL)-10 is a potent anti-inflammatory cytokine. Its role in modulating liver injury induced by galactosamine and lipopolysaccharide (Gal/LPS) was investigated.
The effects of recombinant IL-10 (rIL-10), anti-IL-10 monoclonal antibodies, or gadolinium chloride (GdCl3) pretreatment were studied in mice challenged with Gal/LPS. Tumor necrosis factor (TNF) alpha and IL-10 serum concentrations were measured and liver injury was assessed by alanine aminotransferase (ALT) serum concentrations and by histology.
(1) IL-10 is produced early and together with TNF-alpha after Gal/LPS challenge. (2) Anti-IL-10 pretreatment increases TNF-alpha (+443%, P = 0.04), ALT (+160%, P = 0.04) serum levels, and the percentage of severe necrosis compared with control monoclonal antibodies. (3) Administration of rIL-10 30 minutes before Gal/LPS decreases TNF-alpha (-67%, P = 0.02), ALT (-94%, P = 0.01) serum concentrations, and the proportion of severe necrosis. The hepatoprotective effect is still observed when rIL-10 is injected 30 or 120 minutes after Gal/LPS. (4) GdCl3 pretreatment protects against hepatotoxicity, decreases TNF-alpha, but increases IL-10 serum concentrations.
These results indicate that IL-10 protects the liver in the Gal/LPS mouse model. Increased IL-10 and decreased TNF-alpha secretion are potentially involved in the hepatoprotection observed after GdCl3 pretreatment.
白细胞介素（IL）-10是一种强效抗炎细胞因子。本研究探讨其在调节由半乳糖胺和脂多糖（Gal/LPS）诱导的肝损伤中的作用。
在接受Gal/LPS攻击的小鼠中研究重组IL-10（rIL-10）、抗IL-10单克隆抗体或氯化钆（GdCl3）预处理的效果。测量肿瘤坏死因子（TNF）α和IL-10血清浓度，并通过丙氨酸转氨酶（ALT）血清浓度和组织学评估肝损伤。
（1）在Gal/LPS攻击后，IL-10早期产生并与TNF-α一起产生。（2）与对照单克隆抗体相比，抗IL-10预处理可增加TNF-α（+443%，P = 0.04）、ALT（+160%，P = 0.04）血清水平以及严重坏死的百分比。（3）在Gal/LPS攻击前30分钟给予rIL-10可降低TNF-α（-67%，P = 0.02）、ALT（-94%，P = 0.01）血清浓度以及严重坏死的比例。当在Gal/LPS攻击后30或120分钟注射rIL-10时，仍可观察到肝保护作用。（4）GdCl3预处理可预防肝毒性，降低TNF-α，但增加IL-10血清浓度。
这些结果表明，在Gal/LPS小鼠模型中，IL-10可保护肝脏。IL-10增加和TNF-α分泌减少可能参与了GdCl3预处理后观察到的肝保护作用。
