Acute lung injury and acute kidney injury are established by four hours in experimental sepsis and are improved with pre, but not post, sepsis administration of TNF-α antibodies.
Acute lung injury and acute kidney injury are established by four hours in experimental sepsis and are improved with pre, but not post, sepsis administration of TNF-α antibodies.
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DOI：
10.1371/journal.pone.0079037
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Faubel S
中科院分区：
文献类型：
--
作者：
Bhargava R;Altmann CJ;Andres-Hernando A;Webb RG;Okamura K;Yang Y;Falk S;Schmidt EP;Faubel S
急性肾损伤（AKI）和急性肺损伤（ALI）是脓毒症的严重并发症。 AKI 通常被视为败血症的晚期并发症。值得注意的是，AKI 相对于 ALI 的发病情况尚不清楚，因为肾功能（BUN 和肌酐）的常规测量不敏感，并且会在晚期增加。在这项研究中，我们假设 AKI 和 ALI 由于共同的病理生理学（即 TNF-α 介导的全身炎症反应综合征 [SIRS]）而同时发生，但需要敏感的肾功能标志物来识别 AKI。使用 5 种不同的一次性剂量腹膜内 (IP) 内毒素 (LPS)（0.00001、0.0001、0.001、0.01 或 0.25 mg）或盲肠结扎穿刺 (CLP) 诱导成年雄性 C57B/6 小鼠败血症。通过血清促炎细胞因子（TNF-α、IL-1β、CXCL1、IL-6）评估 SIRS，通过肺部炎症（肺髓过氧化物酶 [MPO] 活性）评估 ALI，通过 4 小时时的血清肌酐、BUN 和肾小球滤过率 (GFR)（通过 FITC 标记的菊粉清除率）评估 AKI。在 IP LPS 之前 2 小时或之后 2 小时，IP 注射 20 µg TNF-α 抗体 (Ab) 或载体。所有 5 剂 LPS 均增加血清细胞因子；分别使用 GFR 和肺部炎症的敏感标记物在 IP LPS 或 CLP 4 小时内检测到 AKI 和 ALI。值得注意的是，肌酐不会随任何剂量而增加； BUN 增加 0.01 和 0.25 mg。值得注意的是，0.001 mg LPS 剂量下的 GFR 降低了 50%，这表明脓毒症时肾功能会急剧丧失，而 BUN 或肌酐没有变化。预防性 TNF-α Ab 降低血清细胞因子、肺 MPO 活性和 BUN；然而，脓毒症后给药没有效果。 ALI 和 AKI 在脓毒症病程早期同时发生，TNF-α 在两者的早期发病机制中发挥作用。
Acute kidney injury (AKI) and acute lung injury (ALI) are serious complications of sepsis. AKI is often viewed as a late complication of sepsis. Notably, the onset of AKI relative to ALI is unclear as routine measures of kidney function (BUN and creatinine) are insensitive and increase late. In this study, we hypothesized that AKI and ALI would occur simultaneously due to a shared pathophysiology (i.e., TNF-α mediated systemic inflammatory response syndrome [SIRS]), but that sensitive markers of kidney function would be required to identify AKI. Sepsis was induced in adult male C57B/6 mice with 5 different one time doses of intraperitoneal (IP) endotoxin (LPS) (0.00001, 0.0001, 0.001, 0.01, or 0.25 mg) or cecal ligation and puncture (CLP). SIRS was assessed by serum proinflammatory cytokines (TNF-α, IL-1β, CXCL1, IL-6), ALI was assessed by lung inflammation (lung myeloperoxidase [MPO] activity), and AKI was assessed by serum creatinine, BUN, and glomerular filtration rate (GFR) (by FITC-labeled inulin clearance) at 4 hours. 20 µgs of TNF-α antibody (Ab) or vehicle were injected IP 2 hours before or 2 hours after IP LPS. Serum cytokines increased with all 5 doses of LPS; AKI and ALI were detected within 4 hours of IP LPS or CLP, using sensitive markers of GFR and lung inflammation, respectively. Notably, creatinine did not increase with any dose; BUN increased with 0.01 and 0.25 mg. Remarkably, GFR was reduced 50% in the 0.001 mg LPS dose, demonstrating that dramatic loss of kidney function can occur in sepsis without a change in BUN or creatinine. Prophylactic TNF-α Ab reduced serum cytokines, lung MPO activity, and BUN; however, post-sepsis administration had no effect. ALI and AKI occur together early in the course of sepsis and TNF-α plays a role in the early pathogenesis of both.
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影响因子：
38.9
作者：
Bagshaw, Sean M.;Bennett, Michael;Bellomo, Rinaldo
通讯作者：
Bellomo, Rinaldo
影响因子：
19.6
作者：
Kim, Duk Hoon;Jung, Yu Jin;Kim, Won
通讯作者：
Kim, Won
影响因子：
13.6
作者：
Doi, Kent;Yuen, Peter S. T.;Star, Robert A.
通讯作者：
Star, Robert A.
影响因子：
4.4
作者：
Cunningham, PN;Wang, Y;Quigg, RJ
通讯作者：
Quigg, RJ
DOI：
10.1186/cc7940
发表时间：
2009
期刊：
Critical care (London, England)
影响因子：
--
作者：
Liu KD;Altmann C;Smits G;Krawczeski CD;Edelstein CL;Devarajan P;Faubel S
通讯作者：
Faubel S