The role of IFN-gamma in the pathology of experimental endotoxemia.
The role of IFN-gamma in the pathology of experimental endotoxemia.
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DOI：
10.4049/jimmunol.145.9.2920
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发表时间：
1990-11
影响因子：
4.4
通讯作者：
F. Heinzel
中科院分区：
文献类型：
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作者：
F. Heinzel
由循环细菌LPS引起的促炎性细胞因子介导许多感染性休克特征性的破坏性宿主反应。为了确定淋巴因子IFN-γ在内毒素休克期间是否具有类似的致病作用，在相对于用沙门氏菌LPS攻击的不同时间用鼠rIFN-γ（rMuIFN-γ）预处理小鼠。当rMuIFN-γ在内毒素攻击之前或之后4小时给药时，随后的死亡率增加。用rMuIFN-γ预处理导致内毒素血症期间血清TNF增加近5倍，但TNF水平不受内毒素后给予IFN的影响。血清TNF水平的增加可能反映了该因子的翻译增强，因为在IFN预处理的小鼠中TNF mRNA的组织表达没有相应增加。为了检查内毒素血症期间内源性产生的IFN-γ的作用，在注射内毒素之前用0.5mg抗IFN-γ mAb预处理小鼠。这种治疗显著降低了内毒素休克的死亡率，但仅引起血清TNF的轻微降低。内毒素后2小时给予抗IFN-γ具有类似的保护作用。这些结果表明IFN-γ在脓毒性休克的病理学中具有重要作用，既间接作为已知促进致死性的单核因子的激活剂，也可能通过其他迟发性机制。
Proinflammatory cytokines provoked by circulating bacterial LPS mediate many of the destructive host responses characteristic of septic shock. To determine if the lymphokine IFN-gamma has a similar pathogenic role during endotoxic shock, mice were pretreated with murine rIFN-gamma (rMuIFN-gamma) at various times relative to challenge with Salmonella enteritidis LPS. Subsequent mortality was increased when rMuIFN-gamma was administered before or up to 4 h after endotoxin challenge. Pretreatment with rMuIFN-gamma resulted in nearly fivefold increases in serum TNF during endotoxemia, but TNF levels were unaffected by IFN administered after endotoxin. The increased levels of serum TNF probably reflected enhanced translation of this factor, as tissue expression of TNF mRNA did not increase correspondingly in IFN-pretreated mice. To examine the role of IFN-gamma produced endogenously during endotoxemia, mice were pretreated with 0.5 mg of anti-IFN-gamma mAb before endotoxin injection. This treatment significantly reduced mortality from endotoxic shock but caused only minor decreases in serum TNF. Anti-IFN-gamma administered 2 h after endotoxin was similarly protective. These results demonstrate a significant role for IFN-gamma in the pathology of septic shock, both indirectly as an activator of monokines known to promote lethality and possibly by other, late-acting mechanisms.