While chronic stress lasting weeks or months tends to weaken the immune system, scientists at Stanford University School of Medicine have found that short-term stress — the flight-or-flight response — actually stimulates it.
Working with colleagues at Stanford and two other universities, Firdaus Dhabhar, Ph.D., an associate professor of psychiatry and behavioral sciences, showed that subjecting laboratory rats to mild stress caused a massive mobilization of several key types of immune cells into the bloodstream and then onto destinations, including the skin and other tissues. This large-scale mobilization is comparable to the mustering of troops in a crisis, Dhabhar said.
The researchers found that the massive redistribution of immune cells was orchestrated by three hormones released by the adrenal glands in response to the stress-inducing event — norepinephrine, epinephrine and corticosterone (the rat analog of cortisol in humans). These hormones are the brain’s call-to-arms to the rest of the body, according to Dhabhar.
“Mother Nature gave us the fight-or-flight stress response to help us, not to kill us,” he said.
In his experiments, Dhabhar subjected the lab rats to mild stress by confining them (gently, and with full ventilation) in transparent Plexiglas enclosures. He drew blood several times over a two-hour period and, for each time point, measured levels of norepinephrine, epinephrine and corticosterone, as well as of several distinct immune-cell types in the blood.
What he saw was a pattern of carefully choreographed changes in blood levels of the three hormones, along with the movement of many different subsets of immune cells from reservoirs such as the spleen and bone marrow into the blood and, finally, to various “front line” organs.
To show that specific hormones were responsible for the movements of specific cell types, Dhabhar administered the three hormones to rats whose adrenal glands had been removed so they couldn’t generate their own stress hormones. When the researchers mimicked the pattern of stress-hormone release previously observed in the confined rats, the same immune-cell migration patterns emerged in the rats without adrenal glands. Placebo treatment produced no such effect, the researchers noted.
The general pattern, Dhabhar said, was that norepinephrine is released early and is primarily involved in mobilizing all major immune-cell types — monocytes, neutrophils and lymphocytes — into the blood. Epinephrine, also released early, mobilized monocytes and neutrophils into the blood, while nudging lymphocytes out into “battlefield” destinations, such as skin. Corticosterone, released somewhat later, caused virtually all immune cell types to head out of circulation to the “battlefields.”
The overall effect of these movements is to bolster immune readiness, the researchers said. A study published by Dhabhar and his colleagues in 2009 in the Journal of Bone and Joint Surgery assessed patients’ recovery from surgery as a function of their immune-cell redistribution patterns during the stress of the operation. Those patients in whom the stress of surgery mobilized immune-cell redistributions similar to those seen in the confined rats in the new study did significantly better afterward than patients whose stress hormones less adequately guided immune cells to appropriate destinations, he said.
This newfound information could lead to medical applications, such as administering low doses of stress hormones or drugs that mimic or antagonize them to optimize patients’ immune readiness for procedures such as surgery or vaccination, Dhabhar said.
“More studies will be required including in human subjects, which we hope to conduct, before these applications can be attempted,” he said.
Closer at hand is the monitoring of patients’ stress-hormone levels and immune-cell distribution patterns during surgery to assess their surgical prognosis, or during immunization to predict vaccine effectiveness, he said.
The latest study was published online in the Journal of Psychoneuroendocrinology.