Critical role for peripherally-derived interleukin-10 in mediating the thermoregulatory manifestations of fever and hypothermia in severe forms of lipopolysaccharide-induced inflammation
Critical role for peripherally-derived interleukin-10 in mediating the thermoregulatory manifestations of fever and hypothermia in severe forms of lipopolysaccharide-induced inflammation
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DOI：
10.1007/s00424-013-1371-4
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发表时间：
2014-07-01
影响因子：
4.5
通讯作者：
Roth, Joachim
中科院分区：
文献类型：
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作者：
Harden, Lois M.;Rummel, Christoph;Roth, Joachim
虽然外周释放的白细胞介素（IL）-10在限制轻度至中度炎症形式的发热中具有关键的调节作用，但其在调节严重炎症期间注意到的体温过低和发热的更复杂的体温调节表现中的作用尚不清楚。使用细胞因子拮抗作用，因此，我们研究了外周释放的IL-10介导的低体温，发热和炎症诱导的腹膜内（IP）管理的大剂量的脂多糖（LPS）的参与。将雄性Wistar大鼠（200-250 g）麻醉并在腹腔内植入温度敏感无线电遥测仪。在IP注射LPS（10 mg/kg）或磷酸盐缓冲盐水（PBS）前4 h，将大鼠随机分配至IP接受IL-10抗血清（IL-10AS）或正常绵羊血清。在IP注射LPS或PBS后90分钟和6小时，在血浆和组织样品（脾、肝和脑）中测量炎症反应。LPS的管理诱导的体温过低的初始阶段（类似于90分钟）后，发热发展。用IL-10 AS预处理大鼠可消除LPS诱导的血浆IL-10水平升高，减轻体温降低，增加发热幅度。此外，IL-10AS预处理增强了LPS诱导的外周血浆肿瘤坏死因子-α（90分钟和6小时）、IL-1 β（90分钟）、前列腺素E-2（90分钟）和IL-6（6小时）水平的升高，但在体温过低和发热期间，下丘脑中没有。内源性IL-10通过其对脾脏和肝脏中炎症介质合成的作用，在严重的缺血性（LPS诱导的）全身性炎症期间介导体温过低和发热中起关键的调节作用。
Although peripherally released interleukin (IL)-10 has a critical regulatory role in limiting fever in mild-to-moderate forms of inflammation, its role in regulating the more complex thermoregulatory manifestations of hypothermia and fever noted during severe inflammation is less clear. Using cytokine antagonism, we therefore investigated the involvement of peripherally released IL-10 in mediating hypothermia, fever and inflammation induced by intraperitoneal (IP) administration of a large dose of lipopolysaccharide (LPS). Male Wistar rats (200-250 g) were anaesthetized and implanted intra-abdominally with temperature-sensitive radiotelemeters. Rats were randomly assigned to receive IL-10 antiserum (IL-10AS) or normal sheep serum IP, 4 h before receiving an IP injection of LPS (10 mg/kg) or phosphate-buffered saline (PBS). Inflammatory responses were measured in plasma and tissue samples (spleen, liver and brain) at 90 min and 6 h after the IP injection of LPS or PBS. Administration of LPS induced an initial period of hypothermia (similar to 90 min) after which fever developed. Pre-treating rats with IL-10AS abolished the LPS-induced increase in plasma IL-10 levels, attenuated the hypothermia and increased the amplitude of the fever. Moreover, IL-10AS pre-treatment augmented the LPS-induced increase in plasma levels of tumor necrosis factor-alpha (90 min and 6 h), IL-1 beta (90 min), prostaglandin E-2 (90 min) and IL-6 (6 h), in the periphery, but not the hypothalamus, over the duration of hypothermia and fever. Via its action on the synthesis of inflammatory mediators in the spleen and liver, endogenous IL-10 plays a crucial regulatory role in mediating hypothermia and fever during severe aspectic (LPS-induced) systemic inflammation.