Stress Leads to Infection In Skin Wounds

Contact: Phillip Marucha, 614-292-1162

Written by Holly Wagner, 614-292-8310[email protected]

STRESS LEADS TO INFECTION IN SKIN WOUNDS, STUDY SUGGESTS

COLUMBUS, Ohio - Stress may increase the chances that a skin wound will become infected, new research suggests.

Researchers found that wounds on mice that were psychologically stressed were more than three times more likely to become infected than were wounds on non-stressed animals.

The study also showed that stress slowed the rate of wound healing by nearly one-third, said Phillip Marucha, a study co-author and an associate professor of periodontology at Ohio State University.

"The response meant to control infection-causing bacteria in the wound wasn't working in the stressed mice," he said. "The stress caused a reaction that ultimately blocked the prompt mending of the tissue."

Their research appears in a recent issue of the journal Brain, Behavior, and Immunity.

The researchers stressed the mice by putting individual animals inside tubes for 15 hours a day and depriving them of access to food and water during that same time period. The animals underwent three days of restraint prior to wounding, followed by an additional five days of restraint.

"The confinement, in addition to the lack of food and water, served as a stressor for the mice. The animals couldn't turn around or move from side to side," Marucha said.

Control mice were allowed to roam free in their cages, but they were also deprived of food and water. Control mice were wounded at the same time as were the confined mice.

Immediately after wounding the mice, the researchers exposed the injuries of some of the animals to a strain of the bacteria Streptococcus. Streptococcus is commonly found on the skin of mice and can cause myriad illnesses in humans, including strep throat and pneumonia.

In order to measure bacterial levels in the wounds, the researchers began sacrificing some mice two hours after inoculating the wounds with Streptococcus and continued to do so from days one through 13.

The researchers removed the wounded area from each sacrificed mouse in order to measure the presence and level of bacteria in the wounds. Eighty-five percent of the wounds of the stressed mice were infected, compared to 27 percent of the wounds of the non-stressed mice.

In addition to Streptococcus, the researchers found a proliferation of opportunistic bacteria - bacteria that cause infection when the immune system is weakened - in the stressed animals. The most prevalent of the opportunistic bacteria were Staphylococcus, particularly S. aureus, the leading cause of hospital-acquired infections in humans.

The total bacteria count in the wounds of the stressed mice was much higher from days five through 13 after Streptococcus application, compared to levels in the control mice. Results showed three-quarters of the wounds in the stressed mice contained bacteria other than Streptococcus, compared to 11 percent of the wounds of the non-stressed mice.

Total bacteria levels peaked about five days after initial wounding. The bacteria levels in the stressed mice were about 100,000 times the amount measured in the wounds of the control mice. "That's an astounding amount," Marucha said.

The wounds on the stressed mice - whether or not Streptococcus had been applied - took 30 percent longer to close than did the wounds in the control mice. But the same bacteria seemed to accelerate wound healing in control mice during the first 24 hours of healing, compared to the non-inoculated control mice.

"Bacteria contain toxins that stimulate inflammation, and inflammation is an immune system mechanism that causes wounds to close at a faster rate," Marucha said. "The added bacteria could only enhance healing when the innate immune response was intact.

"Stress disrupts the body's equilibrium, in turn significantly impairing its ability to control and eradicate bacterial infection during wound healing," he said. "The bottom line was that stress shut down either the recruitment or the function of those immune cells needed to fight infection."

This research was supported by a grant from the National Institute of Dental and Craniofacial Research, part of the National Institutes of Health.

Marucha co-authored the study with David Padgett, an assistant professor of oral biology; John Sheridan, a professor of oral biology; and Isolde-Gina Rojas, an oral biology student in Marucha's laboratory.

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