Stress can give the immune system a beneficial boost

New research in mice provides more evidence that a brief bout of stress can give the immune system a beneficial boost – under certain conditions.

Laboratory results showed that acute stress – stress that lasts for minutes to hours – temporarily mobilized all major types of immune cells, or leukocytes to potential battle stations in the body. In certain situations, this stress-induced boost in the number of immune cells may be advantageous, as leukocytes fight infections and other diseases.

Stressed mice had much higher numbers of leukocytes arriving at critical defense organs, such as the skin, than did non-stressed mice.

"Acute stress could help increase immune protection," said Firdaus Dhabhar, the study's lead author and an associate professor of oral biology and molecular virology, immunology and medical genetics at Ohio State University. "An increase in leukocyte activity and availability may enhance the immune system's ability to protect the body during surgery, vaccination or during an infection".

But there is also a downside – ushering an increased number of immune cells to sites of potential immune reaction could worsen pre-existing inflammatory illnesses such as cardiovascular disease or gingivitis, and autoimmune disorders such as arthritis, multiple sclerosis or psoriasis. In autoimmune diseases, the immune system attacks the body.

"Understanding mechanisms that mobilize leukocytes to potential battle stations during stress could help us figure out ways to boost the immune response when it could be most helpful to do so, such as during surgery, vaccination or infection,” Dhabhar said. “And it could also help us tone down the immune response during inflammatory diseases.”

Dhabhar and Kavitha Viswanathan, a graduate research associate in oral biology at Ohio State, reported their findings online in the Proceedings of the National Academy of Sciences.

The current study is one of a number of studies conducted by researchers at Ohio State that look at the effects of stress on the immune system. While Dhabhar and his team have focused on the effects of acute stressors, other researchers have found that chronic stress may substantively weaken the immune system.

Leukocytes are always present in the body, but most remain dormant until an immune response is activated by wounding or infection or until the brain identifies a stressful situation. When that happens, the brain releases hormones that set troops of these immune cells into motion. The cells travel to potential battle stations – primarily the skin along with the lymph nodes that drain the skin.

“Most immune challenges or wounds involve on the skin or other epithelial linings of the body,” Dhabhar said. “If nothing happens immunologically following stress – the skin isn’t cut or wounded in some other way – activated leukocytes usually return to their resting position in a few hours.”

Some of the mice in the study were restrained in clear plastic ventilated tubes for two-and-a-half hours. These mice – the stressed group – could not turn around in the tube, but they could move forward and backward. This restraint created a brief spell of psychological stress, similar to the kind of stress a person anticipating or undergoing a dental or surgical procedure may feel. The other group of mice – the non-stressed group – remained in their home cages.

Once the stressed mice were removed from the tubes, the researchers implanted tiny sponges underneath the skin on the backs of all of the animals, including the mice in the non-stressed group. These disc-shaped sponges were about the size of a grain of rice.

Sponges were removed from some of the mice six hours after implantation and from the rest of the mice one, two or three days later. The researchers compared the numbers of leukocytes in each sponge once the sponges were removed.

“Just one session of acute stress caused a significant increase in the numbers of leukocytes to collect in the sponge,” Dhabhar said. Indeed, the amount of certain types of immune cells had increased by 200 to 300 percent in the stressed mice.

By that third day, the number of leukocytes that had collected in the sponges of the stressed mice had declined and was similar to the number of cells that had collected in the sponges of the non-stressed animals.

Prior to their implantation, the sponges were soaked in either saline or one of two proteins that the body produces during an immune response. These proteins, called lymphotactin (LTN) and TNF-alpha, attract different types of leukocytes.

After sponges were removed from the mice, the researchers also analyzed the types and quantity of specific immune cells attracted to each of the proteins.

“While all major leukocytes are mobilized in great numbers at the first hints of acute stress, the immune proteins that are generated at the battle site will determine which types of immune cells are further recruited in greater numbers,” Dhabhar said.

“Different types of immune challenges may produce different cocktails of immune proteins,” he continued. “Knowing how the body’s stress hormones work with these kinds of proteins to recruit immune cells could help us develop therapeutic interventions to regulate how a person’s immune system responds to different challenges.”

Grants from the National Institutes of Health and the Dana Foundation supported this work.