ACUTE PSYCHOLOGICAL STRESS PROMOTES SKIN HEALING IN MICE
Brief, acute
psychological stress promoted healing in mouse models of three different types
of skin irritations, in a study led by UC San Francisco researchers.
The scientists found
that healing was brought about by the anti-inflammatory effects of
glucocorticoids -- steroid hormones -- produced by the adrenal glands in
response to stress.
"Under chronic
stress, these same naturally-occurring steroids damage the protective functions
of normal skin and inhibit wound healing, but during shorter intervals of
stress, they are beneficial for inflammatory disorders and acute injury in both
mice and humans," said senior investigator Peter Elias, MD, a UCSF
professor of dermatology based at the San Francisco VA Medical Center (SFVAMC).
"We believe that
our findings explain why this otherwise harmful component of the stress
response has been preserved during human evolution," he said.
The study was
published online in the Journal of Investigative Dermatology on
August 7, 2014, in advance of print publication in the journal.
The scientists studied
mouse models of three types of common skin irritations: irritant contact
dermatitis, caused by exposure to an irritant such as a soap or solvent; acute
allergic contact dermatitis, of the sort caused by poison ivy or poison oak; and
atopic dermatitis, or eczema.
After exposure to
irritants on a small patch of skin on one ear, one group of mice was returned
to its regular cages, while another group was put in a stressful situation --
being placed in very small enclosures for 18 hours a day over the course of
four days.
The researchers found
that the stressed mice showed significantly reduced inflammation and faster
healing in all three types of skin irritation.
When stressed mice
were simultaneously given mifepristone, which blocks steroid action, all of the
healing benefits of stress disappeared. "This demonstrated the central
role of internal steroids in providing these benefits," said Elias.
He noted that other
researchers have recently proposed that psychological stress has a potential
role in promoting healing, "but that work has focused on the immune system
rather than glucocorticoids as the responsible, beneficial mediator."
According to Elias,
the study provides a clue to an evolutionary puzzle: why, over millions of
years, humans have preserved the tendency to produce steroids under stress.
Previous research by Elias's laboratory and others has demonstrated that
prolonged exposure to steroids harms both the structure and function of skin
and other organs.
"Our ancestors
did not have an arsenal of pharmaceutical steroids available to treat acute
illnesses or injuries," Elias observed. "This safe, effective
internal anti-inflammatory system provides just the correct amount of steroids
to promote healing, over a time interval that is too short to cause harm."
Elias emphasized that
the study did not look at the implications for human medical treatments.
However, he contrasted the "substantial benefits" seen from modest
increases in glucocorticoid levels brought on by short-term stress with the
"adverse effects that we see all too commonly" with steroid therapy.
Elias speculated that those negative effects could be the result of
"overly aggressive treatment -- too high doses, and perhaps for
unnecessarily prolonged treatment intervals."
He said that while his
research team did not study other kinds of inflammatory disorders, "the
same benefits of psychological stress should accrue in any acute illness or
injury."
Co-authors of the
study are Mao-Qiang Man, MD, of SFVAMC and UCSF; Juan-Luis Santiago, MD, of
SFVAMC, UCSF, and Hospital General Universitario del Ciudad Real, Spain;
Melanie Hupe of SFVAMC and UCSF; Gemma Martin-Ezquerra, MD, of Hospital del
Mar-IMIM, Barcelona, Spain; Jong-Kyum Youm, PhD, and Tammy Zhai of SFVAMC and
UCSF; Carles Trullas, PhD, of ISDIN, Barcelona; and Kenneth R. Feingold, MD, of
SFVAMC and UCSF.
The study was funded
by the SFVAMC and the National Institutes of Health.
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