Kozak W, Poli V, Soszynski D, Conn C A, Leon L R, Kluger M J
Institute for Basic and Applied Medical Research, The Lovelace Institutes, Albuquerque, New Mexico 87108, USA.
Am J Physiol. 1997 Feb;272(2 Pt 2):R621-30. doi: 10.1152/ajpregu.1997.272.2.R621.
Interleukin-6 (IL-6), among other cytokines, is thought to be involved in the regulation of sickness behavior (e.g., anorexia, cachexia, fever, and lethargy) induced by infections bacterial and viral origin) and sterile tissue necrosis (burns and surgical traumas). Mice deficient in IL-6 (IL-6 KO) were generated by gene targeting. Homozygous IL-6 KO male and female mice and their appropriate controls were implanted with biotelemeters to monitor body temperature (Tb) and motor activity (Act). Normal circadian rhythms in Tb and Act as well as rates of food intake and weight gain did not differ significantly between sex-matched IL-6 KO and control groups at 30 degrees C in a 12:12-h light-dark cycle. Sterile tissue damage was induced in mice by subcutaneous injection of turpentine (0.1 ml, left hindlimb). Influenza pneumonitis was induced by intranasal inoculation of mouse-adapted influenza A virus (17.5 plaque-forming units). Lack of IL-6 completely prevented fever, anorexia, and cachexia because of turpentine abscess in both sexes. It did not prevent lethargy, although IL-6 KO mice recovered to normal Act significantly sooner than wild-type mice. Symptoms of sickness were only slightly modified during influenza virus infection in IL-6 KO mice. Attenuation of sickness behavior was more pronounced in IL-6 KO female than in male mice. We conclude that, although IL-6 is induced during both turpentine abscess and influenza infection, this cytokine appears to be more critical in induction of the symptoms of sickness behavior during sterile tissue abscess than during influenza infection.
白细胞介素-6（IL-6）与其他细胞因子一样，被认为参与了由细菌和病毒感染以及无菌性组织坏死（烧伤和手术创伤）诱导的疾病行为（如厌食、恶病质、发热和嗜睡）的调节。通过基因靶向技术构建了IL-6基因缺陷（IL-6 KO）小鼠。将纯合IL-6 KO雄性和雌性小鼠及其相应对照植入生物遥测器，以监测体温（Tb）和运动活动（Act）。在12:12小时明暗循环、30摄氏度条件下，性别匹配的IL-6 KO组和对照组之间，Tb和Act的正常昼夜节律以及食物摄入量和体重增加率没有显著差异。通过皮下注射松节油（0.1 ml，左后肢）在小鼠中诱导无菌性组织损伤。通过鼻内接种小鼠适应的甲型流感病毒（17.5个噬斑形成单位）诱导流感肺炎。缺乏IL-6完全预防了两性因松节油脓肿引起的发热、厌食和恶病质。虽然IL-6 KO小鼠比野生型小鼠恢复到正常Act的时间明显更早，但它并没有预防嗜睡。在IL-6 KO小鼠感染流感病毒期间，疾病症状仅有轻微改变。IL-6 KO雌性小鼠的疾病行为减轻比雄性小鼠更明显。我们得出结论，虽然在松节油脓肿和流感感染期间都会诱导产生IL-6，但这种细胞因子在无菌性组织脓肿期间诱导疾病行为症状方面似乎比在流感感染期间更为关键。
