Reduced leptin levels in starvation increase susceptibility to endotoxic shock
Reduced leptin levels in starvation increase susceptibility to endotoxic shock
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DOI：
10.1016/s0002-9440(10)65049-3
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发表时间：
2000-05-01
影响因子：
6
通讯作者：
Grunfeld, C
中科院分区：
文献类型：
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作者：
Faggioni, R;Moser, A;Grunfeld, C
营养不良损害免疫功能，降低对感染的抵抗力。我们研究是否减少瘦素诱导饥饿增加易感性脂多糖（LPS）和肿瘤坏死因子（TNF）诱导的致死性。在小鼠中，禁食48小时增强对LPS的敏感性，通过给予瘦素减少禁食诱导的瘦素下降显著降低对LPS的敏感性。虽然禁食降低基础瘦素水平，LPS治疗增加瘦素在相同的程度，在喂养的动物。空腹增加基础血清皮质酮，瘦素治疗钝化这种增加。禁食降低了LPS升高皮质酮的能力;瘦素恢复了皮质酮对LPS的反应。瘦素治疗既不影响基础血糖，也不影响LPS后，LPS诱导禁食小鼠血清TNF增加5倍，瘦素替代使其减弱。与此相反，LPS诱导较低水平的干扰素-γ和白细胞介素-1 β在禁食相比，喂养的动物没有差异;瘦素对这些细胞因子没有影响。此外，禁食增加了对TNF本身的致死作用的敏感性，这也被瘦素治疗逆转。因此，瘦素似乎通过抑制LPS诱导的TNF和降低TNF毒性来保护。
Malnutrition compromises Immune function, reducing resistance to infection. We examine whether the decrease in leptin induced by starvation increases susceptibility to lipopolysaccharide (LPS)- and tumor necrosis factor (TNF)-induced lethality. In mice, fasting for 48 hours enhances sensitivity to LPS, Decreasing the fasting-induced fall in leptin by leptin administration markedly reduced sensitivity to LPS. Although fasting decreases basal leptin levels, LPS treatment increased leptin to the same extent as in fed animals. Fasting increased basal serum corticosterone; leptin treatment blunted this increase. Fasting decreased the ability of LPS to increase corticosterone; leptin restored the corticosterone response to LPS, Serum glucose levels were decreased in fasted mice and LPS induced a further decrease. Leptin treatment affected neither basal glucose nor that after LPS, LPS induced a fivefold greater increase in serum TNF in fasted mice, which was blunted by leptin replacement. In contrast, LPS induced lower levels of interferon-gamma and no differences in interleukin-1 beta in fasted compared to fed animals; leptin had no effect on those cytokines. Furthermore, fasting increased sensitivity to the lethal effect of TNF itself, which was also reversed by leptin treatment. Thus, leptin seems to be protective by both inhibiting TNF induction by LPS and by reducing TNF toxicity.