Michie H R, Eberlein T J, Spriggs D R, Manogue K R, Cerami A, Wilmore D W
Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115.
Ann Surg. 1988 Oct;208(4):493-503. doi: 10.1097/00000658-198810000-00011.
The cytokine interleukin-2 is a primary modulator of the immune response that occurs after infection, trauma, and transplant rejection, yet its role as a mediator of associated metabolic changes in surgical illness is unknown. We studied clinical and metabolic responses in eleven tumor-bearing humans with normal renal and hepatic function receiving bolus intravenous (I.V.) interleukin-2 (30,000 U/kg). Additional subjects (n = 6) were pretreated with the cyclooxygenase inhibitor, ibuprofen (1600 mg, orally), before interleukin-2 administration. Serial measurements were made of vital signs, symptoms, hematology, and plasma concentrations of pituitary and stress hormones and selected cytokines. Administration of interleukin-2 resulted in fever, tachyacardia, "flu-like" symptoms, and neurohormonal elaboration. The responses observed were quantitatively similar to those that occurred after endotoxin administration in healthy subjects (n = 13), but differed in the following manner: 1) the onset of fever and endocrine changes occurred after a longer latent interval (180-240 minutes vs. 60-90 minutes after endotoxin), 2) peak responses after the administration of interleukin-2 also occurred later, 3) no increased circulating tumor necrosis factor was detected after administration of interleukin-2 (peak plasma concentration was greater than 35 pg/ml vs. 270 +/- 70 pg/ml after endotoxin administration), and 4) administration of interleukin-2 but not of endotoxin was associated with increased circulating concentrations of gamma interferon (peak plasma concentration 1.7 +/- 0.2 NIH U/ml vs. less than 0.1 NIH U/ml after endotoxin administration). Fever and neurohormonal responses after interleukin-2 administration were greatly attenuated by ibuprofen administration. Interleukin-2 induces other cytokines that exert their effects largely through the cyclooxygenase pathway. Interleukin-2 may be an important signal, initiating the integrated host responses to infection and injury.
细胞因子白细胞介素 -2 是感染、创伤及移植排斥后发生的免疫反应的主要调节因子，但其作为外科疾病相关代谢变化的介质的作用尚不清楚。我们研究了 11 名肾功能和肝功能正常的荷瘤患者静脉推注白细胞介素 -2（30,000 U/kg）后的临床和代谢反应。另外 6 名受试者在给予白细胞介素 -2 之前口服环氧化酶抑制剂布洛芬（1600 mg）进行预处理。对生命体征、症状、血液学、垂体和应激激素以及选定细胞因子的血浆浓度进行了连续测量。给予白细胞介素 -2 导致发热、心动过速、“流感样”症状以及神经激素分泌增加。观察到的反应在数量上与健康受试者（n = 13）给予内毒素后发生的反应相似，但在以下方面有所不同：1）发热和内分泌变化的发作在较长的潜伏期后出现（分别为 180 - 240 分钟和内毒素后 60 - 90 分钟），2）给予白细胞介素 -2 后的峰值反应也出现得较晚，3）给予白细胞介素 -2 后未检测到循环肿瘤坏死因子增加（血浆峰值浓度大于 35 pg/ml，而内毒素给药后为 270 +/- 70 pg/ml），4）给予白细胞介素 -2 而非内毒素与循环γ干扰素浓度增加有关（血浆峰值浓度为 1.7 +/- 0.2 NIH U/ml，而内毒素给药后小于 0.1 NIH U/ml）。布洛芬给药可大大减轻给予白细胞介素 -2 后的发热和神经激素反应。白细胞介素 -2 诱导其他细胞因子，这些细胞因子主要通过环氧化酶途径发挥作用。白细胞介素 -2 可能是一个重要信号，启动宿主对感染和损伤的综合反应。
