Interleukin 12, interferon gamma, and tumor necrosis factor alpha are the key cytokines of the generalized Shwartzman reaction.
Interleukin 12, interferon gamma, and tumor necrosis factor alpha are the key cytokines of the generalized Shwartzman reaction.
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DOI：
10.1084/jem.180.3.907
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发表时间：
1994-09-01
期刊：
影响因子：
--
通讯作者：
Garotta G
中科院分区：
文献类型：
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作者：
Ozmen L;Pericin M;Hakimi J;Chizzonite RA;Wysocka M;Trinchieri G;Gately M;Garotta G
Shwartzman反应是通过在小鼠中两次注射脂多糖（LPS）引起的。在足垫中给予引发LPS注射，而致死LPS激发在24小时后静脉内给予。注射干扰素γ（IFN-γ）或白细胞介素12（IL-12）代替LPS引发注射诱导进一步用LPS攻击的小鼠的致死反应。当与引发剂一起给予时，抗IFN-γ的抗体防止了用LPS、IL-12或IFN-γ引发的小鼠中的致死反应。当与引发剂一起给予时，抗IL-12的抗体阻止了用LPS或IL-12引发的小鼠的致死反应，但不能阻止IFN-γ。这些结果强烈表明LPS诱导IL-12的释放，IL-12诱导IFN-γ的产生，并且IFN-γ是引发巨噬细胞和其他细胞类型的细胞因子。在LPS攻击后，通过大量产生作用于已经被IFN-γ致敏的靶位点的炎性细胞因子诱导致死性Shwartzman反应。如果使用TNF和IL-1的混合物或TNF和IFN-γ的混合物来攻击先前用IFN-γ或IL-12致敏的小鼠，则诱导死亡。在相同条件下，单个细胞因子或IL-1和IFN-γ的混合物不能代替LPS攻击。当用LPS致敏小鼠时，TNF、IL-1和IFN-γ的组合仅诱导部分死亡率，这表明其他LPS诱导的因子的参与。
The Shwartzman reaction is elicited by two injections of lipopolysaccharide (LPS) in mice. The priming LPS injection is given in the footpad, whereas the lethal LPS challenge is given intravenously 24 h later. The injection of interferon gamma (IFN-gamma) or interleukin 12 (IL-12) instead of the LPS priming injection induced the lethal reaction in mice further challenged with LPS. Antibodies against IFN- gamma when given together with the priming agent, prevented the lethal reaction in mice primed with either LPS, IL-12, or IFN-gamma. Antibodies against IL-12, when given together with the priming agent, prevented the lethal reaction in mice primed with either LPS or IL-12 but not with IFN-gamma. These results strongly suggest that LPS induces the release of IL-12, that IL-12 induces the production of IFN-gamma, and that IFN-gamma is the cytokine that primes macrophages and other cell types. Upon LPS challenge, the lethal Shwartzman reaction is induced by a massive production of inflammatory cytokines that act on the target sites already sensitized by IFN-gamma. If mixtures of TNF and IL-1 or mixtures of TNF and IFN-gamma are used to challenge mice previously primed with IFN-gamma or IL-12, mortality is induced. In the same conditions, the individual cytokines or a mixture of IL-1 and IFN- gamma do not replace the LPS challenge. When the mice are primed with LPS, the combination of TNF, IL-1, and IFN-gamma induced only a partial mortality incidence suggesting that the involvement of other LPS- induced factors.