IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses
IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses
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DOI：
10.1172/jci1368
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发表时间：
1998-01-15
影响因子：
15.9
通讯作者：
Achong, MK
中科院分区：
文献类型：
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作者：
Xing, Z;Gauldie, J;Achong, MK
IL-6通常与促炎性细胞因子TNF α和IL-1一起在许多警报条件下被诱导，并且循环IL-6在急性期反应的诱导中起重要作用。然而，这种内源性IL-6是否在局部或全身反应中发挥任何额外的促或促作用仍不清楚。本研究采用IL-6+/+和IL-6-/-小鼠建立内毒素肺或内毒素血症动物模型，研究IL-6在急性炎症反应中的作用。内毒素的气溶胶暴露诱导IL-6+/+小鼠肺中IL-6和促炎细胞因子TNF α和MIP-2的增加以及嗜酸性反应。然而，IL-6-/-小鼠肺中TNF α和MIP-2的水平以及嗜中性粒细胞的水平显著较高。这些小鼠的中性粒细胞凋亡率与IL-6+/+小鼠相似。低组成性水平的IL-10细胞因子不被内毒素增强，并且在IL-6+/+和IL-6-/-小鼠的肺中保持相似。全身性地，腹膜内递送内毒素导致IL-6-/-小鼠中TNF α、MIP-2、GM-CSF和IFN γ的循环水平比IL-6+/+小鼠中显著得多，并且向IL-6-/-小鼠施用重组IL-6消除了这些差异。相反，在IL-6+/+和IL-6-/-小鼠中，循环IL-10水平被诱导至相似程度。因此，我们的研究表明，内源性IL-6通过控制促炎性细胞因子而不是促炎性细胞因子的水平，在局部和全身急性炎症反应中起着至关重要的调节作用，并且IL-10或其他IL-6家族成员不能补偿IL-6的这些调节活性。
IL-6 is induced often together with the proinflammatory cytokines TNF alpha and IL-1 in many alarm conditions, and circulating IL-6 plays an important role in the induction of acute phase reactions. However, whether this endogenous IL-6 plays any additional pro-or antiinflammatory roles in local or systemic responses remains unclear. In this study, the role of IL-6 in acute inflammatory responses was investigated in animal models of endotoxic lung or endotoxemia by using IL-6+/+ and IL-6-/- mice. Aerosol exposure of endotoxin induced increased IL-6 and proinflammatory cytokines TNF alpha and MIP-2 and a neutrophilic response in the lung of IL-6+/+ mice. However, the levels of TNF alpha and MIP-2 and neutrophilia were significantly higher in the lung of IL-6-/- mice. The rate of neutrophil apoptosis in these mice was similar to that in IL-6+/+ mice. A low constitutive level of antiinflammatory cytokine IL-10 was not enhanced by endotoxin and remained similar in the lung in both IL-6+/+ and IL-6-/- mice. Systemically, intraperitoneal delivery of endotoxin resulted in much more pronounced circulating levels of TNF alpha, MIP-2, GM-CSF, and IFN gamma in IL-6-/- mice than in IL-6+/+ mice, and administration of recombinant IL-6 to IL-6-/- mice abolished these differences. In contrast, circulating IL-10 levels were induced to a similar degree in both IL-6+/+ and IL-6-/- mice. Thus, our studies reveal that endogenous IL-6 plays a crucial antiinflammatory role in both local and systemic acute inflammatory responses by controlling the level of proinflammatory, but not antiinflammatory, cytokines, and that these antiinflammatory activities by IL-6 cannot be compensated for by IL-10 or other IL-6 family members.