A Little Stress May Go A Long Way Toward Boosting Skin's Immunity

The immune response of animals exposed to acute stress – about two hours of restraint – was two to four times higher compared to non-stressed animals. This was true when the animals' skin was treated with chemical or protein antigens immediately after a stressful event. An antigen is any substance that the immune system reacts to by producing cells and antibodies.

Stress plus exposure to the antigen triggered an immune response that remained strong for weeks to several months later, when the animals were re-exposed to the irritant without further restraint.

"Acutely stressed animals had a much more vigorous immune response when they were first exposed to the antigen," said Firdaus Dhabhar, an associate professor of oral biology and molecular virology, immunology and medical genetics at Ohio State University.

"That boost to immunity seemed to last, as these animals' immune systems also showed a powerful response when re-exposed to the antigen much later."

Control animals showed a normal immune response to the antigen upon re-exposure, but nowhere near that of the animals that had been stressed.

Dhabhar will give an overview of a decade's worth of research on the effects of acute stress on skin immunity on February 10 at the annual American Academy of Dermatology meeting in Washington, D.C.

In several laboratory studies, researchers compared the immune responses of rats and mice that were restrained for two hours immediately before exposure to the antigen to control animals that were not restrained.

"Gentle restraint, or confinement, creates psychological stress," Dhabhar said. "As a result, heart rate increases, as do blood pressure and circulating levels of stress hormones. All are characteristic signs of a normal stress response, and all subside within a few hours after the stressful situation ends."

The researchers assessed the magnitude of immune responses by measuring the degree of inflammation at the initial site of antigen administration. They examined the types of cells and proteins – indicators of immune system activity – that were present, and in what amounts.

Animals were exposed to the same antigen, this time at a different place on the body, a few weeks to several months later. The researchers again measured immune responses.

"The stressed animals had a much more powerful immune response to the antigen, compared to the non-stressed animals," Dhabhar said. "And the stressed animals' immune systems continued to stay strong, too, as shown by the later tests."

Short-term stress had boosted the animals' immune responses two to four times over the response of the non-stressed mice, an effect the researchers saw when the animals were first exposed to the antigen. The researchers saw the same results when animals were again exposed to the antigen a few weeks to several months later.

"The more robust initial immune reaction might have formed a more efficient, or larger, pool of memory cells that ultimately gave the stressed animals' immune systems a continued immune advantage months later," Dhabhar said.

Memory cells "remember" a specific antigen – a substance that the immune system reacts to by forming cells and antibodies. Years and even decades later memory cells can launch an intense attack against the same antigen.

Dhabhar likens the body's immune response to waging a war: Soldiers, in the form of immune cells and proteins, travel from the barracks (the spleen) through blood-vessel boulevards to potential battle stations in the skin. This process speeds up during brief bouts of stress.

"During both the initial and secondary exposures, the stressed animals' immune responses occurred at a faster rate and were significantly elevated for several days compared to control animals," Dhabhar said, adding that while this effect may be beneficial for healing a wound and fighting infections, it could also spell trouble for people with skin allergies or inflammatory disorders such as eczema, dermatitis, psoriasis and arthritis.

"In many of these diseases, the immune system attacks the body and causes inflammation and other serious problems," Dhabhar said. "Anything that boosts the immune response can cause more damage. But learning how the immune system mobilizes these inflammation-causing cells could possibly help scientists develop therapeutic targets for such diseases."

Learning how the body mobilizes an immune response during stress could also give researchers insight into creating more effective vaccines.

"The whole point of vaccination is to generate more memory cells," Dhabhar said. "The way the stressed animals' immune systems responded to the antigen the second time around suggests that acute stress may help generate more of these memory cells.

"Most people believe that stress weakens the immune system and increases susceptibility to infection, yet the benefits of acute stress make sense from an evolutionary standpoint," he said. "Short-term stress activates protective biological mechanisms that are essential for survival."

Support for this work came from the National Institutes of Health and The Dana Foundation Clinical Hypotheses Program in Mind Body Medicine.