Mild hypothermia promotes pro-inflammatory cytokine production in monocytes
Mild hypothermia promotes pro-inflammatory cytokine production in monocytes
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DOI：
10.1097/01.ana.0000188639.39844.f6
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发表时间：
2006-07-01
影响因子：
3.7
通讯作者：
Maekawa, Tsuyoshi
中科院分区：
文献类型：
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作者：
Matsui, Tomohiro;Ishikawa, Toshizo;Maekawa, Tsuyoshi
体温过低通常与宿主防御受损和感染有关。已经研究了与低温相关的免疫功能的恶化，但是细胞因子在宿主防御机制和感染中的参与仍然不清楚。我们以前已经表明，轻度低温修改外周血单核细胞产生细胞因子。在这项研究中，低温对单核细胞产生的几种细胞因子和一氧化氮（NO）的影响进行了测定。将从10名健康人获得的单核细胞与脂多糖（LPS）在低温（33 ℃）或常温（37 ℃）条件下培养48小时。我们进行流式细胞术分析，同时测量培养上清液中的白细胞介素（IL）-8，IL-1 β，IL-6，IL-10，IL-12 p70和肿瘤坏死因子（TNF）-α。通过比色测定将NO产生定量为培养基中亚硝酸盐的积累。与常温相比，亚低温升高了LPS刺激单核细胞产生的IL-1 β、IL-6、IL-12 p70和TNF-α的水平。然而，在计算这些升高的细胞因子与IL-10的比率时，只有IL-12 p70/IL-10和TNF-α/IL-10比率在低温条件下显著升高。相反，低温不影响NO的产生。这项研究表明，轻度低温影响单核细胞产生的细胞因子的平衡，导致促炎状态。具体而言，单核细胞IL-12和TNF-α似乎参与了在轻度低温下观察到的免疫改变。然而，这些现象的临床意义仍有待澄清。
Hypothermia is often associated with compromised host defenses and infection. Deteriorations of immune functions related to hypothermia have been investigated, but the involvement of cytokines in host defense mechanisms and in infection remains unclear. We have previously shown that mild hypothermia modifies cytokine production by peripheral blood mononuclear cells. In this study, the effects of hypothermia on the monocytic production of several cytokines and nitric oxide (NO) were determined. Monocytes obtained from 10 healthy humans were cultured with lipopolysaccharide (LPS) under hypothermic (33 degrees C) or normothermic (37 degrees C) conditions for 48 hours. We performed flow cytometric analysis for simultaneous measurement of interleukin (IL)-8, IL-1 beta, IL-6, IL-10, IL-12p70, and tumor necrosis factor (TNF)-alpha in culture supernatants. NO production was quantified as accumulation of nitrite in the medium by a colorimetric assay. Compared with normothermia, mild hypothermia raised the levels of IL-1 beta, IL-6, IL-12p70, and TNF-alpha produced by monocytes stimulated with LPS. On calculating the ratios of these elevated cytokines to IL-10, however, only IL-12p70/IL-10 and TNF-alpha/IL-10 ratios were significantly elevated under hypothermic conditions. In contrast, hypothermia did not affect NO production. This study demonstrates that mild hypothermia affects the balance of cytokines produced by monocytes, leading to a pro-inflammatory state. Specifically, monocytic IL-12 and TNF-alpha appear to be involved in the immune alterations observed in mild hypothermia. However, the clinical significance of these phenomena remains to be clarified.