Villa P, Demitri M T, Meazza C, Sironi M, Gnocchi P, Ghezzi P
Mario Negri Institute for Pharmacological Research, Milano, Italy.
Eur Cytokine Netw. 1996 Dec;7(4):765-9.
The effects of methyl palmitate (MP), a known inhibitor of Kupffer cells, were studied in a model of polymicrobial sepsis induced in CD-1 mice by cecal ligation and puncture (CLP). The inhibition of Kupffer cells by pretreatment with MP was shown by the reduced phagocytosis, the production of tumor necrosis factor (TNF) and interleukin-6 (IL-6) after lipopolysaccharide (LPS) challenge. The reduced activation of Kupffer cells resulted in lower levels of inflammatory products after CLP. TNF and IL-6 were significantly reduced in serum 2 h and 24 h respectively after CLP, interleukin-1 beta (IL-1 beta) was reduced in liver 4 h after CLP, nitric oxide (NO) and serum amyloid A (SAA) were significantly reduced 8 and 24 h respectively after CLP. Liver toxicity was significantly reduced in MP-treated mice and survival was significantly prolonged at all intervals, reaching 45% after six to ten days compared with 3% in control mice. These findings suggest that Kupffer cells play an important role in liver damage and survival in sepsis.
在通过盲肠结扎和穿刺（CLP）诱导的CD-1小鼠多微生物败血症模型中，研究了已知的库普弗细胞抑制剂棕榈酸甲酯（MP）的作用。用MP预处理对库普弗细胞的抑制作用表现为脂多糖（LPS）刺激后吞噬作用降低、肿瘤坏死因子（TNF）和白细胞介素-6（IL-6）产生减少。库普弗细胞激活的降低导致CLP后炎症产物水平降低。CLP后2小时和24小时血清中TNF和IL-6分别显著降低，CLP后4小时肝脏中白细胞介素-1β（IL-1β）降低，CLP后8小时和24小时一氧化氮（NO）和血清淀粉样蛋白A（SAA）分别显著降低。MP处理的小鼠肝脏毒性显著降低，所有时间段的存活率均显著延长，六至十天后达到45%，而对照小鼠为3%。这些发现表明，库普弗细胞在败血症的肝损伤和存活中起重要作用。
