Bautista A P, Fletcher D J, Volkman A
Department of Pathology, East Carolina University School of Medicine, Greenville, North Carolina.
Lab Invest. 1989 Mar;60(3):447-54.
The administration of a potent activator of macrophages (M phi), Propionibacterium acnes, in nondiabetic mice was associated with the release of significant amounts of interleukin-1 (IL-1) in the peritoneal cavity and plasma within 4 hours after treatment. Shortly before IL-1 peaks were observed, the levels of pancreatic insulin, [3H]leucine-proinsulin, and insulin/total protein ratio were elevated, and followed by a transient but marked hyperinsulinemia at 4 hours after treatment. A single dose of recombinant murine IL-1 in mice was also associated with a 2- to 9-fold increase in the levels of insulin in the pancreas and plasma at 4 hours after treatment. During the period of observation after the administration of P. acnes, plasma glucose levels in treated mice were significantly less than in parallel controls. Mild hypoglycemia was observed at 7 to 10 days posttreatment. Although circulating IL-1-like activity could not be detected in plasma 1 to 10 days after P. acnes treatment, this activity was measured in activated peritoneal and liver M phi. IL-1-like activity (specific activity: 276 units/mg protein) was detected in plasma, after it was chromatographed on a Sephadex G-150 column to remove proteins with higher molecular weight. Peritoneal and liver M phi from P. acnes mice were also able to elaborate significant amounts of IL-1-like activity in their supernatants with or without Escherichia coli lipopolysaccharide. At the same time, total protein synthesis and insulin content in the pancreas in P. acnes mice were significantly lower than the parallel control (p less than 0.01). These results suggest that P. acnes-induced M phi activation in mice was associated with the modulation of insulin release and glucose homeostasis which may be attributed to the accumulation and release of IL-1 by activated M phi.
在非糖尿病小鼠中给予巨噬细胞（M phi）的强效激活剂痤疮丙酸杆菌后，在治疗后4小时内腹腔和血浆中会释放大量白细胞介素-1（IL-1）。在观察到IL-1峰值前不久，胰腺胰岛素、[3H]亮氨酸-胰岛素原水平以及胰岛素/总蛋白比值升高，随后在治疗后4小时出现短暂但显著的高胰岛素血症。给小鼠单次注射重组鼠IL-1后，治疗后4小时胰腺和血浆中胰岛素水平也会升高2至9倍。在给予痤疮丙酸杆菌后的观察期内，治疗组小鼠的血浆葡萄糖水平显著低于平行对照组。在治疗后7至10天观察到轻度低血糖。尽管在痤疮丙酸杆菌治疗后1至10天血浆中未检测到循环IL-1样活性，但在活化的腹腔和肝脏M phi中检测到了这种活性。在血浆经Sephadex G-150柱层析以去除高分子量蛋白质后，检测到了IL-1样活性（比活性：276单位/毫克蛋白）。来自痤疮丙酸杆菌处理小鼠的腹腔和肝脏M phi在有或没有大肠杆菌脂多糖的情况下，其培养上清液中也能产生大量IL-1样活性。同时，痤疮丙酸杆菌处理小鼠胰腺中的总蛋白合成和胰岛素含量显著低于平行对照组（p < 0.01）。这些结果表明，痤疮丙酸杆菌诱导的小鼠M phi激活与胰岛素释放和葡萄糖稳态的调节有关，这可能归因于活化的M phi积累和释放IL-1。
