Age-associated differences in TNF-alpha and nitric oxide production in endotoxic mice.
Age-associated differences in TNF-alpha and nitric oxide production in endotoxic mice.
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DOI：
10.4049/jimmunol.156.4.1525
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发表时间：
1996-02
影响因子：
4.4
通讯作者：
B. B. Chorinchath-B.;L. Kong;L. Mao;R. Mccallum
中科院分区：
文献类型：
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作者：
B. B. Chorinchath-B.;L. Kong;L. Mao;R. Mccallum
革兰氏阴性细菌感染是美国老年人群中脓毒性休克的常见原因。我们采用脓毒症实验模型来研究老年动物中LPS致死率增加的原因。用细菌LPS处理三个年龄的雄性B6 JC 3 J/Nia小鼠，年轻（2月龄）、成熟（12月龄）和衰老（24月龄），发现老年小鼠对LPS致死性的敏感性高10倍。衰老小鼠对LPS的敏感性增加与血浆TNF-α和一氧化氮水平显著升高相关。针对TNF-α的抗体为老年动物提供了针对超致死剂量LPS的被动保护，从而确立了TNF在老年动物对LPS敏感性增加中的核心作用。其他细胞因子，如IL-1和IFN-γ，出现继发于TNF和一氧化氮的年龄相关的敏感性LPS。血浆皮质酮水平增加LPS的时候，血浆TNF-α的最大水平，观察到在两个年龄组，虽然激素的生产和TNF-α释放的幅度不同的年龄组之间的动力学。外源性给予地塞米松保护衰老的动物给予高剂量的LPS，通过降低细胞因子水平。因此，在老年动物中观察到的对LPS的敏感性增加似乎是由于TNF和一氧化氮产生过量，这是由细胞因子产生的内源性激素控制受到干扰引起的。
Gram-negative bacterial infection is a common cause of septic shock in the older population in the U.S. We employed an experimental model of sepsis to study the cause of increased lethality due to LPS in older animals. Three ages of male B6JC3J/Nia mice, young (2 mo old), mature (12 mo old), and senescent (24 mo old), were treated with bacterial LPS, and the older mice were found to be 10 times more sensitive to LPS lethality. Increased sensitivity to LPS in senescent mice correlated with significantly elevated plasma TNF-alpha and nitric oxide levels. Abs to TNF-alpha afforded aged animals passive protection against a supralethal dose of LPS, establishing a central role for TNF in the increased sensitivity to LPS seen in the aged animals. Other cytokines, such as IL-1 and IFN-gamma, appeared secondary to TNF and nitric oxide in the age-associated sensitivity to LPS. Plasma corticosterone levels were increased by LPS at a time when maximal levels of plasma TNF-alpha were observed in both age groups, although the kinetics of hormone production and the magnitude of TNF-alpha release varied among the age groups. Exogenously administered dexamethasone protected senescent animals given a high dose of LPS, by decreasing cytokine levels. The increased sensitivity to LPS observed in aged animals, therefore, seems to be due to excessive TNF and nitric oxide production, resulting from perturbed endogenous hormonal control of cytokine production.