Effects of hemorrhage on cytokine gene transcription.
Effects of hemorrhage on cytokine gene transcription.
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发表时间：
1993-08
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通讯作者：
R. Shenkar;Edward Abraham
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作者：
R. Shenkar;Edward Abraham
损伤和失血通常伴随着感染和器官系统功能障碍的快速发展，通常累及粘膜部位，如肺和肠道。为了研究导致这些情况的可能机制，我们使用半定量聚合酶链式反应来检测在30%出血量失血后1小时后复苏的预定时间点从小鼠粘膜和系统解剖部位分离的细胞群体中细胞因子mRNA的表达。在出血后1小时内，肺实质内单个核细胞中IL-1α、IL-1β、IL-5和转化生长因子-β的mRNA水平显著升高。肺泡巨噬细胞中转化生长因子-β转录水平在失血后1小时升高，IL-1α转录水平在失血后2小时开始升高。在出血后4小时内，Peyer‘s斑块细胞中IL-1β、IL-2、IL-5、IL-6、干扰素-γ和转化生长因子-β的mRNA水平显著升高。肠系膜淋巴结分离的细胞在失血后4小时内，IL-1β、肿瘤坏死因子-α和转化生长因子-β的mRNA水平显著升高。在出血后的任何时间点，脾细胞或外周血单核细胞中大多数细胞因子的mRNA表达没有明显变化。这些实验表明，失血即使复苏，最早在出血后1小时就会显著增加促炎症和免疫调节细胞因子基因的转录。这些出血后细胞因子mRNA表达的改变在粘膜部位尤为显著，这表明在严重失血和损伤后肺和肠道参与器官系统衰竭的发生率增加的机制。
Injury and blood loss are often followed by infection and the rapid development of organ system dysfunction, frequently involving mucosal sites, such as the lung and intestine. To examine possible mechanisms contributing to these conditions, we used semiquantitative polymerase chain reactions to determine cytokine mRNA expression among cellular populations isolated from mucosal and systemic anatomic sites of mice at predetermined time points following 30% blood volume hemorrhage with resuscitation 1 hr later. Within 1 hr after hemorrhage, significant increases were observed in mRNA levels for IL-1 alpha, IL-1 beta, IL-5, and TGF-beta in intraparenchymal pulmonary mononuclear cells. The levels of TGF-beta transcripts among alveolar macrophages were increased 1 hr following blood loss, and increase in IL-1 alpha transcripts was found starting 2 hr posthemorrhage. Cells from Peyer's patches showed significant increases in mRNA levels for IL-1 beta, IL-2, IL-5, IL-6, IFN-gamma, and TGF-beta during the 4 hr following hemorrhage. Significant increases in mRNA levels for IL-1 beta, TNF-alpha, and TGF-beta were present within 4 hr of blood loss among cells isolated from mesenteric lymph nodes. The expression of mRNA for most cytokines was not significantly altered in splenocytes or peripheral blood mononuclear cells at any time point following hemorrhage. These experiments demonstrate that blood loss, even if resuscitated, produces significant increases in proinflammatory and immunoregulatory cytokine gene transcription as early as 1 hr following hemorrhage. These posthemorrhage alterations in cytokine mRNA expression were particularly prominent at mucosal sites, suggesting a mechanism for the increased incidence of pulmonary and intestinal involvement in organ system failure following severe blood loss and injury.