June 22, 1998 COLUMBUS, Ohio -- A new study of dental students found that stress can lengthen the time wounds take to heal by as much as 40 percent and reduce by two-thirds the production of one cytokine -- interleukin-1 -- that is integral for the healing process.
The study, published in the current issue of the journal Psychosomatic Medicine, is the latest advance in nearly two decades of research here into the effects even common stress has on the human immune system.
The study also showed that this stress-induced slow-down of the healing process seems to occur in the first few days after injury. Researchers believe this suggests that additional supportive therapies applied soon after injuries might counteract the slowing effects caused by stress.
The study by Phillip Marucha, associate professor of periodontology; Janice Kiecolt-Glaser, professor of psychiatry and psychology; and Mehrdad Favagehi, a former graduate student, also has important implications for how fast surgery patients can recover from their wounds.
Marucha and Kiecolt-Glaser discovered in an earlier study that the rate of wound-healing on the outer skin can be slowed by common stressors. In this latest project, they wanted to focus on mucosal tissue, such as that in the mouth.
“The nice thing about an oral wound,” Marucha said, “is that it generally heals without scarring and it does so quickly -- sometimes at two to three times the rate of other skin wounds.”
Eleven dental students signed up for this project. Each student received their first small wound to the palette -- 3.5 millimeters -- in late summer between their first and second year. Daily photographs were taken of each wound using a video camera and these images were digitized and analyzed by computer.
The wounds were also swabbed daily with hydrogen peroxide beginning on the fifth day after wounding. Once the peroxide swabbing failed to produce bubbling at the wound site for two days, the wound was considered healed.
At the same time as the wounding, the students were asked to fill out a short questionnaire intended to gauge their current levels of stress. Blood samples were also drawn from the students at the same time to measure the level of certain biochemical markers as a gauge of how well the immune system was working.
The whole process was then repeated about six weeks later just before the students faced their first major examinations of the school year. Marucha said the exams were tough since the courses were very hard and these were the first classes they shared with medical students.
“These were particularly stressful for the dental students,” Marucha said.
The study showed the wounds received just before exams took an average of 40 percent longer to heal than those in the summer, suggesting that even the stress of test-taking was enough to alter the process. “These students were experienced test-takers and weren’t prone to simple ‘test anxiety,’” Marucha said.
An analysis of the students’ blood showed that levels of interleukin-1 had dropped by two-thirds in the second test, compared to those during the summer experiments.
Interleukin-1 is an important cytokine that plays several major roles in the immune response: It increases the number of adhesion molecules required for wounds to close; it stimulates the inflammation process to ward off infection; and it stimulates keratinocyte growth -- cells that help form a tough layer over wounds.
The findings match well with a related project John Sheridan, professor of oral biology at Ohio State, just reported in the journal Brain, Behavior, and Immunity. Along with David Padgett, an adjunct assistant of oral biology , and Marucha, they compared the rates of wound healing using a small hairless mouse.
“In the mouse, we looked histologically at the wound sites as they were healing and found that in mice that were stressed, inflammatory cells were just not getting to the sites,” Marucha said. “We have a two- to three-fold reduction in the number of inflammatory cells at the wound site in the mouse model, which correlates well” with the human study, he said.
The researchers believe the findings are clinically significant.
“We should be able to work more successfully to try to modify their stress levels either pharmacologically, biologically or psychologically.”
Marucha also said the study is also important because wound-healing plays a vital role in how the body responds to every infection we get, regardless of its location. Enhancing wound-healing should improve our treatment of infections.
The research was supported in part by the National Institutes of Health and the National Institute of Dental Research.
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