Sepsis chronically in MARS: systemic cytokine responses are always mixed regardless of the outcome, magnitude, or phase of sepsis.
Sepsis chronically in MARS: systemic cytokine responses are always mixed regardless of the outcome, magnitude, or phase of sepsis.
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DOI：
10.4049/jimmunol.1201806
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发表时间：
2012-11-01
期刊：
影响因子：
--
通讯作者：
Remick DG
中科院分区：
文献类型：
--
作者：
Osuchowski MF;Craciun F;Weixelbaumer KM;Duffy ER;Remick DG
从sirs到cars的转变模式表明，过度炎症会引发急性脓毒症死亡，而脓毒症晚期的低炎症（释放抗炎细胞因子）会导致慢性死亡。然而，脓毒症结果的确切体液炎症机制仍然难以捉摸。在研究的第一部分中，我们描述了CLP败血症死亡（DIE）和存活（SUR）小鼠（6-28天）慢性炎症的全身动力学。在第二部分中，我们结合当前的慢性和以前的急性/慢性脓毒症数据来比较这两个阶段之间的结果依赖性炎症特征。为了比较整体炎症反应，计算了复合细胞因子评分（CCS）。小鼠不处死，每天取20μl血样。第一部分：将慢性死亡小鼠的参数聚集到死亡前72h、48h和24h时间点，并与clp后同一天的SUR进行比较。细胞因子的增加是混合的，并且从未在48小时之前导致慢性死亡（增加3至180倍）。在慢性死亡前24小时，CCS显示出促炎室和抗炎室同时和类似的上调（与SUR相比，DIE分别高出80和50倍）。第二部分：脓毒症各阶段/结局的细胞因子比率显示稳定的pro-vs。抗炎的平衡。CCS显示慢性死亡小鼠的炎症反应比急性死亡小鼠低5倍，但与急性SUR相同。综上所述，系统性的mars样模式（促炎性和抗炎性细胞因子的同时释放）与脓毒症的阶段、反应强度和/或结果无关。虽然程度不同，但急性和慢性脓毒症死亡率与血液中主要的促炎性和/或抗炎性特征无关。
The paradigm of SIRS-to-CARS transition implies that hyperinflammation triggers acute sepsis mortality, while hypoinflammation (release of anti-inflammatory cytokines) in late sepsis induces chronic deaths. However, the exact humoral inflammatory mechanisms attributable to sepsis outcomes remain elusive. In part I of the study, we characterized the systemic dynamics of the chronic inflammation in dying (DIE) and surviving (SUR) mice suffering from CLP sepsis (days 6-28). In part II, we combined the current chronic and previous acute/chronic sepsis data to compare the outcome-dependent inflammatory signatures between these two phases. To compare global inflammatory responses, a composite cytokine score (CCS) was calculated. Mice were never sacrificed but sampled daily (20μl) for blood. Part I: parameters from chronic DIE mice were clustered into the 72h, 48h and 24h prior-to-death time-points and compared to SUR of the same post-CLP day. Cytokine increases were mixed and never preceded chronic deaths earlier than 48h (3 to 180-fold increase). CCS demonstrated simultaneous and similar upregulation of pro-and anti-inflammatory compartments at 24h prior to chronic death (DIE 80 and 50-fold higher vs. SUR). Part II: cytokine ratios across sepsis phases/outcomes indicated steady pro-vs. anti-inflammatory balance. CCS showed the inflammatory response in chronic DIE was 5-fold lower versus acute DIE mice, yet identical to acute SUR. Concluding, the systemic MARS-like pattern (concurrent release of pro-and anti-inflammatory cytokines) occurs irrespectively of the sepsis phase, response magnitude and/or outcome. Although different in magnitude, neither acute nor chronic septic mortality is associated with a predominating pro-and/or anti-inflammatory signature in the blood.
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影响因子：
120.7
作者：
Boomer, Jonathan S.;To, Kathleen;Chang, Kathy C.;Takasu, Osamu;Osborne, Dale F.;Walton, Andrew H.;Bricker, Traci L.;Jarman, Stephen D., II;Kreisel, Daniel;Krupnick, Alexander S.;Srivastava, Anil;Swanson, Paul E.;Green, Jonathan M.;Hotchkiss, Richard S.
通讯作者：
Hotchkiss, Richard S.
DOI：
10.4049/jimmunol.1001567
发表时间：
2011-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Belikoff BG;Hatfield S;Georgiev P;Ohta A;Lukashev D;Buras JA;Remick DG;Sitkovsky M
通讯作者：
Sitkovsky M
影响因子：
3.8
作者：
Andaluz-Ojeda, David;Bobillo, Felipe;Bermejo-Martin, Jesus F.
通讯作者：
Bermejo-Martin, Jesus F.
影响因子：
3.1
作者：
Lee, Chien-Chang;Chen, Shey-Ying;Hsueh, Po-Ren
通讯作者：
Hsueh, Po-Ren
影响因子：
82.9
作者：
通讯作者：
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