ter Steege J C, Forget P P, Buurman W A
Department of Pediatrics, Academic Hospital Maastricht, The Netherlands.
Shock. 1999 Feb;11(2):115-9. doi: 10.1097/00024382-199902000-00008.
Enhanced intestinal nitric oxide production observed during sepsis is thought to play a central role in lipopolysaccharide-induced intestinal damage. In contrast intestinal polyamines, both from endogenous and exogenous origin, are essential for the maintenance of mucosal integrity. Polyamines have been shown to inhibit lipopolysaccharide-induced nitric oxide release in vitro and have been claimed to exert additional antiinflammatory actions. In this study, the effect of the polyamine spermine on the release of the proinflammatory mediators nitric oxide and tumor necrosis factor-alpha by a murine macrophage cell line was investigated. Furthermore, we investigated whether oral spermine administration inhibits lipopolysaccharide-induced intestinal inducible nitric oxide synthase and nitrotyrosine expression and modulates the release of inflammatory mediators. Our results show that although spermine inhibited lipopolysaccharide-induced nitric oxide release in a murine macrophage cell line, no effect on tumor necrosis factor-alpha release was observed. In addition, oral spermine administration inhibited intestinal inducible nitric oxide synthase and nitrotyrosine expression suggesting a protective effect of spermine on lipopolysaccharide-induced intestinal damage. In parallel a decrease in serum levels of the proinflammatory mediators nitrate, nitrite, and interferon-gamma and an increase in the antiinflammatory cytokine interleukin-10 was observed, although tumor necrosis factor-alpha levels were unaffected. These results indicate that spermine inhibits lipopolysaccharide-induced nitric oxide release in vitro as well as in vivo. Further, intraluminally derived polyamines modulate the systemic immune response. It is concluded that oral spermine administration might have therapeutic perspectives for several disorders characterized by systemic inflammation and intestinal damage.
脓毒症期间观察到的肠道一氧化氮生成增强被认为在脂多糖诱导的肠道损伤中起核心作用。相比之下，内源性和外源性的肠道多胺对于维持黏膜完整性至关重要。多胺已被证明在体外可抑制脂多糖诱导的一氧化氮释放，并被认为具有额外的抗炎作用。在本研究中，研究了多胺精胺对小鼠巨噬细胞系促炎介质一氧化氮和肿瘤坏死因子-α释放的影响。此外，我们研究了口服精胺是否能抑制脂多糖诱导的肠道诱导型一氧化氮合酶和硝基酪氨酸表达，并调节炎症介质的释放。我们的结果表明，虽然精胺在小鼠巨噬细胞系中抑制了脂多糖诱导的一氧化氮释放，但未观察到对肿瘤坏死因子-α释放有影响。此外，口服精胺抑制了肠道诱导型一氧化氮合酶和硝基酪氨酸表达，提示精胺对脂多糖诱导的肠道损伤具有保护作用。同时，观察到促炎介质硝酸盐、亚硝酸盐和干扰素-γ的血清水平降低，抗炎细胞因子白细胞介素-10增加，尽管肿瘤坏死因子-α水平未受影响。这些结果表明，精胺在体外和体内均能抑制脂多糖诱导的一氧化氮释放。此外，腔内来源的多胺可调节全身免疫反应。得出的结论是，口服精胺给药可能对几种以全身炎症和肠道损伤为特征的疾病具有治疗前景。
