The "black box" of how psychological stress increases susceptibility to infection has been unlocked in a study in the mouse model. The mechanism of action is not through the adaptive immune system, as many had thought, but rather through the secretion of endogenous glucocorticoids that in turn affect the production of two key antimicrobial peptides (AMPs) made by the epidermis.
National report - The "black box" of how psychological stress increases susceptibility to infection has been unlocked in a mouse model study. The mechanism of action is not through the adaptive immune system, as many had thought, but rather through the secretion of endogenous glucocorticoids that, in turn, affect the production of two key antimicrobial peptides (AMPs) made by the epidermis.
Previous work had established that psychological stress decreases the production of lamellar bodies in the secretion of lipids important for the barrier function of skin, Dr. Elias told Dermatology Times.
The two AMPs were readily detected in the outer epidermis of mice at baseline. He then subjected the animals to the psychological stress of sleep deprivation for 48 hours, using lights and noise to keep them awake. He looked again for the two proteins, and levels of both had dropped significantly.
Dr. Elias repeated the experiment but in place of psychological stress, he substituted first systemic injections and later topical administration of glucocorticoids, and found the same results.
Building upon previous work from Dr. Gallo's lab that showed that CRAMP knockout mice had increased susceptibility to group A Streptococcus pyogenes skin infection, researchers compared the results of exposing wild type animals to the pathogen under stressed and non-stressed conditions.
The mean lesion size of the stressed mice was almost twice that of the control animals, and abscesses persisted longer. Most importantly, inhibition of either glucocorticoid action or production normalized the ability of AMPs to restrict those infections.
"Basically, we've shown that the negative effects of stress on epidermal barrier skin integrity and antimicrobial defense are all mediated by glucocorticoids," Dr. Elias says. "Through glucocorticoids, psychological stress downregulates production of epidermal antimicrobial peptides, the distal-most outposts of the innate immune system. If you block glucocorticoid production, you normalize AMP expression and defense against cutaneous infectious challenge."
Dr. Elias believes much of dermatology has been preoccupied with "things immunologic that have distracted us from the principle functions of the skin, which are its protective functions, including permeability barrier function and antimicrobial defenses."