An animal study: profound physiological effects of stress

Stress Reveals Connections Between the Brain and the Blood
Steven Dubovsky, MD reviewing Heidt T et al. Nat Med 2014 Jul.
Chronic unpredictable stress has profound physiologic effects.

It is well known that chronic stress, especially if it is unpredictable, promotes inflammation. To learn more, researchers conducted a series of experiments in mice and 29 medical residents.

The residents self-reported higher stress levels and had higher peripheral neutrophil, monocyte, and lymphocyte counts during their intensive care rotation than at baseline.

Compared with nonstressed controls, mice stressed for 3 weeks had similar blood-count findings as humans; these increases were associated with increased proliferation of bone-marrow stem cells that were differentiating into white cells. Stem cell proliferation was linked to norepinephrine activity in sympathetic nerves innervating blood vessels in bone marrow, apparently via a β3-adrenergic (but not a β2) receptor. In atherosclerosis-prone mice, stress increased macrophage progenitors in bone marrow, and this increased protease levels, inflammation, and cytokines in atherosclerotic plaques. These changes led to rupture-prone plaques.


Acting through the sympathetic nervous system, unpredictable stress appears to mobilize bone-marrow leukocyte progenitors, resulting in a greater number of circulating inflammatory cells that act on atherosclerotic plaques to promote rupture, a primary mechanism of myocardial infarction and stroke. If plaques are not yet well established and damaged, reducing stress might reduce the risk for catastrophic vascular changes. Later in the course of stress-related illness, specific β3 antagonists or perhaps anti-inflammatory drugs might prove helpful. Clinicians should be aware of the profound physiologic effects of stress in their patients.

Editor Disclosures at Time of Publication

Heidt T et al. Chronic variable stress activates hematopoietic stem cells. Nat Med 2014 Jul; 20:754. (
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