Nickerson M, Elphick G F, Campisi J, Greenwood B N, Fleshner M
Dept. of Integrative Physiology, Neuroimmunophysiology Laboratory, Univ. of Colorado, Boulder, CO 80309, USA.
Am J Physiol Regul Integr Comp Physiol. 2005 Dec;289(6):R1665-74. doi: 10.1152/ajpregu.00601.2004. Epub 2005 Aug 4.
Physically active rats have facilitated heat shock protein 72 (Hsp72) responses after stressor exposure in both brain and peripheral tissues compared with sedentary rats. This study verifies that physically active animals do not have elevated Hsp72 levels compared with sedentary animals in the hypothalamus, pituitary, or dorsal vagal complex. We then examined whether 1) physically active rats respond more efficiently than sedentary rats to a bacterial challenge; 2) peripheral immune challenge elicits brain induction of Hsp72; 3) this induction is facilitated by prior freewheel running; and 4) Hsp72 upregulation produced by peripheral immune challenge results in a commensurate decrease in the proinflammatory cytokine IL-1beta. Adult male Fischer 344 rats were housed with either a mobile or locked running wheel. Six weeks later, rats were injected intraperitoneally with saline or Escherichia coli and killed 30 min, 2.5 h, 6 h, and 24 h later. Serum endotoxin and IL-1beta, and peritoneal fluid endotoxin and E. coli colony-forming units (CFUs) were measured. Hsp72 and IL-1beta were measured in hypothalamus, pituitary, and dorsal vagal complex. The results were that physically active rats had a faster reduction in endotoxin and E. coli CFUs and lower levels of circulating endotoxin and cytokines compared with sedentary rats. E. coli challenge elicited significantly greater time-dependent increases of both Hsp72 and IL-1beta in hypothalamus, pituitary, and dorsal vagal complex of physically active animals but not sedentary animals. Contrary to our hypothesis, increases in Hsp72 were positively correlated with IL-1beta. This study extends our findings that physical activity facilitates stress-induced Hsp72 to include immunological stressors such as bacterial challenge and suggests that brain Hsp72 and IL-1beta responses to peripheral immune challenge may contribute to exercise-mediated resistance to long-term sickness.
与久坐不动的大鼠相比，身体活跃的大鼠在应激源暴露后，其大脑和外周组织中的热休克蛋白72（Hsp72）反应更易被诱导。本研究证实，与久坐不动的动物相比，身体活跃的动物在下丘脑、垂体或迷走神经背核中的Hsp72水平并未升高。然后，我们研究了：1）身体活跃的大鼠是否比久坐不动的大鼠对细菌攻击反应更有效；2）外周免疫攻击是否会引发大脑中Hsp72的诱导；3）先前的自由轮跑步是否会促进这种诱导；4）外周免疫攻击产生的Hsp72上调是否会导致促炎细胞因子IL-1β相应减少。成年雄性Fischer 344大鼠被安置在可移动或锁定的跑轮上。六周后，大鼠腹腔注射生理盐水或大肠杆菌，并在30分钟、2.5小时、6小时和24小时后处死。测量血清内毒素和IL-1β，以及腹腔液内毒素和大肠杆菌菌落形成单位（CFU）。在下丘脑、垂体和迷走神经背核中测量Hsp72和IL-1β。结果表明，与久坐不动的大鼠相比，身体活跃的大鼠内毒素和大肠杆菌CFU的减少更快，循环内毒素和细胞因子水平更低。大肠杆菌攻击在身体活跃的动物而非久坐不动的动物的下丘脑、垂体和迷走神经背核中引发了Hsp72和IL-1β更显著的时间依赖性增加。与我们的假设相反，Hsp72的增加与IL-1β呈正相关。本研究扩展了我们的发现，即身体活动促进应激诱导的Hsp7增加，使其包括诸如细菌攻击等免疫应激源，并表明大脑Hsp72和IL-1β对外周免疫攻击的反应可能有助于运动介导的对长期疾病的抵抗力。
