Herfarth H H, Mohanty S P, Rath H C, Tonkonogy S, Sartor R B
Department of Medicine, University of North Carolina, Chapel Hill 27599-7080, USA.
Gut. 1996 Dec;39(6):836-45. doi: 10.1136/gut.39.6.836.
Interleukin 10 (IL10) inhibits monocyte/macrophage and T lymphocyte effector functions. This study examined the effect of systemically administered IL10 on acute and chronic granulomatous enterocolitis, hepatitis, and arthritis in a rat model.
Lewis rats were injected intramurally with streptococcal peptidoglycan-polysaccharide (PG-APS) polymers. Beginning 12 hours before PG-APS injection, rats were treated daily with subcutaneous murine recombinant IL10 or vehicle for three or 17 days.
IL10 attenuated acute enterocolitis in a dose dependent fashion (p < 0.01). Protective effects were more profound in the chronic granulomatous phase with decreased enterocolitis and markedly inhibited leucocytosis, hepatic granulomas, and chronic erosive arthritis (p < 0.001). IL10 downregulated tissue IL1, IL6, tumour necrosis factor alpha, and interferon gamma gene expression, consistent with the in vitro effects of IL10 on PG-APS-stimulated splenocytes. Caecal IL1 protein concentrations and IL2 and interferon gamma secretion by in vitro stimulated mesenteric lymph nodes were downregulated in IL10 treated animals.
These results indicate that exogenous IL10 can inhibit experimental granulomatous inflammatory responses and suggest that IL10 treatment could be an effective new therapeutic approach in human disorders such as Crohn's disease, rheumatoid arthritis, and sarcoidosis.
白细胞介素10（IL10）可抑制单核细胞/巨噬细胞及T淋巴细胞的效应功能。本研究在大鼠模型中检测了全身给予IL10对急性和慢性肉芽肿性小肠结肠炎、肝炎及关节炎的影响。
向Lewis大鼠肠壁内注射链球菌肽聚糖-多糖（PG-APS）聚合物。在注射PG-APS前12小时开始，大鼠每日皮下注射鼠重组IL10或赋形剂，持续3天或17天。
IL10以剂量依赖方式减轻急性小肠结肠炎（p<0.01）。在慢性肉芽肿期，保护作用更为显著，小肠结肠炎减轻，白细胞增多、肝肉芽肿及慢性侵蚀性关节炎明显受到抑制（p<0.001）。IL10下调组织IL1、IL6、肿瘤坏死因子α及干扰素γ基因表达，这与IL10对PG-APS刺激的脾细胞的体外作用一致。在接受IL10治疗的动物中，盲肠IL1蛋白浓度以及体外刺激的肠系膜淋巴结分泌的IL2和干扰素γ均下调。
这些结果表明外源性IL10可抑制实验性肉芽肿性炎症反应，并提示IL10治疗可能是治疗人类疾病如克罗恩病、类风湿性关节炎及结节病的一种有效的新治疗方法。
