Stress May Increase Long-Term Success of Vaccinations

Holly Wagner, Ohio State Unive

PureInsight | June 6, 2005

COLUMBUS , Ohio – The latest study in a series of Ohio State University research projects looking at the differences between acute and chronic stress suggests that acute, or short-term, stress may actually increase a vaccine's effectiveness.

Results from laboratory tests in the current study showed that mice that were psychologically stressed for a short period of time – about two hours – prior to an immunization had significantly better immune responses than non-stressed mice when both groups of animals were re-exposed to the same antigen several months later.

"A brief feeling of stress at the time of immunization may enhance the immune system's long-term memory for an antigen," 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.

"This enhanced immune response is likely to mean greater protection even further down the road," he said.

Researchers think that acute stress – stress that lasts from minutes to hours – may prime the immune system for oncoming trauma.

"In the case of skin wounds and infections, this kind of stress may improve immune function," Dhabhar said. "It may be nature's way of ensuring that the immune system provides heightened protection when we face possible injury or infection."

The study appears online in the "Articles in Press" section of the American Journal of Physiology – Regulatory, Integrative and Comparative Physiology. Dhabhar conducted the study with Kavitha Viswanathan, a doctoral student in oral biology.
The current study is one of a number of studies conducted by researchers at Ohio State that examines how stress affects the immune system. While Dhabhar and his team have focused on the effects of acute stressors, he and other researchers have found that chronic stress may substantively weaken the immune system.

Some of the mice in the current study were restrained in ventilated wire mesh restrainers for two-and-a-half hours. This restraint created a brief spell of psychological stress, similar to the kind of anxiety a person anticipating an injection may feel. The rest of the mice – the non-stressed group – remained in their home cages.

At the end of the restraint period, all of the restrained mice were immunized with an antigen called keyhole limpet hemocyanin (KLH). An antigen is a substance that stimulates an immune response.

A group of non-restrained, non-stressed mice was also immunized with KLH. And a third group of mice was neither immunized nor stressed.

Nine months later, the researchers injected KLH into one earlobe of every mouse in the study. They measured earlobe thickness, and took tissue sections from each lobe in order to count the total number of two types of immune cells – macrophages and lymphocytes. Both types of cells are crucial for mounting an immune response.
Earlobe thickness of the stressed, immunized mice was nearly double that of the mice in the other two groups. The researchers also found that stressed mice had much higher numbers of macrophages and lymphocytes, as well as other kinds of immune cells and proteins in their skin, and higher numbers of memory T-cells in their lymph nodes. T-cells are immune cells that destroy targeted pathogens.

The fact that the previously stressed animals had thicker earlobes – a result of the elevated levels of immune cells responding to KLH – suggests that these mice had required greater immunological memory which resulted in a stronger and faster immune reaction than seen in the other groups of mice.

"It's important to note that this enhancement was seen nine months after a single stress session was experienced during primary immunization," Dhabhar said. "Nine months represents a significant portion of the animal's life span, and the immune-enhancing effects may last much longer than that."

In addition to vaccination, this kind of immune enhancement may provide a higher degree of protection in the case of wounds and infection. The researchers are now working on ways to harness the seemingly beneficial effects of acute stress.
"It would be extremely helpful if we could somehow capture the body's natural, health-promoting defense mechanisms to fight disease and restore health," Dhabhar said. "These studies were conducted in mice and more work needs to be done to extrapolate them to humans. We hope that this study lays a foundation for designing interventions that would stimulate or simulate a natural acute stress response during times like vaccinations."

Grants from the National Institutes of Health and the Dana Foundation supported the current study.


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