The Effect of Stress on the Nervous System and the Immune System

Reference: Ganta, C. K., Blecha, F., Ganta, R. R., Helwig, B. G., Parimi, S., Lu, N., Fels, R. J., Musch, T. I., & Kenney, M. J. (2004). Hyperthermia-enhanced splenic cytokine gene expression is mediated by the sympathetic nervous system. Physiological Genomics, 19(2), 175–183.

Have you ever felt like too much stress made you weak or sick? Researchers have started to explore the biological link between stress and health. In this post, I explore two experiments that suggest a relationship between stress and the immune system.

Experiment 1: Earliest Evidence of a Relationship between Stress and Susceptibility to Infections

Over 140 years ago, in 1879, Louis Pasteur conducted an experiment in which he exposed a group of chickens to anthrax, a bacterium that causes serious infection in cattle. He observed that these chickens did not catch the infection – they were immune to it (1).

However, when the chickens were first exposed to some kind of stressor (e.g., being drenched in ice-cold water) prior to anthrax exposure, they were no longer immune to anthrax infection.

What made the chickens susceptible to the infection in the second case?

The answer is stress.

Yes, stress can do that to chickens, and it can do a lot to you too!

This phenomenon is an example of a topic in PsychoNeuroImmunology; a science that tries to understand the precise mechanisms in which one’s psychological status affects their immunological state. This effect is mediated through our nervous system.

Experiment 2: Stress’s Effect on the Immune System

More recently, researcher Chanran Ganta and his team at Kansas State University performed an interesting experiment proving a precise molecular relationship between the activity of the sympathetic nervous system and immune system functionality.

The sympathetic nervous system (SNS) is a branch of the nervous system that gets activated whenever we are in a dangerous or stressful situation. It creates a “stress response” (sometimes called “fight or flight”), which happens by:

–              Increasing heart rate, so that all the organs of our body receive proper blood circulation

–              Increasing breathing rate to increase oxygen levels

–              Causing an adrenaline surge

–              Halting less-essential processes of the body, such as digestion and sleep

This activation of the SNS gets the body in an active and alert state.

Studying the intricacies of the SNS under stressful situations can help scientists understand how stress affects our physiological functions.

Location of the spleen. Source: Wikipedia.

And this is precisely what Ganta and his team did. They subjected some rats to whole body hyperthermia, or excessive heat. This high heat acted as a stressor and activated their sympathetic nervous system. This allowed the researchers to study the effect of the activated sympathetic system on the spleen, a small immune organ inside your left rib cage, just above the stomach. The spleen stores and filters blood and makes white blood cells for immune protection.

In their experiment, they had two sets of rats: One set had their splenic nerve intact whereas the other set had their splenic nerve denervated – that is, the nerve that connects the nervous system to the spleen was removed.

The research team observed three important outcomes:

  1. An increase in sympathetic discharge was seen in the spleen of rats subjected to hyperthermia, suggesting that excessive heat activated the sympathetic nervous system and directly signaled the spleen through a process called innervation.
  2. The sympathetic discharge affected the spleen. In the rats subjected to hyperthermia, there was an increase in certain cytokines, or immunological molecules that are crucial in controlling the growth and activity of other immune system cells and blood cells.
  3. In the rats that had their splenic nerve removed (i.e., denervated), no increase in cytokines was observed following hyperthermia, suggesting that the splenic nerve plays a vital role in cytokine expression.

These results show that hyperthermia-induced activation of the sympathetic nervous system led to a splenic discharge that altered cytokine levels. Put simply, these results suggest the direct influence of an activated SNS over an immune organ.

Can chronic psychological stress elicit a similar response?

The negative effects of chronic stress on organs such as the heart, digestive system, and brain have been thoroughly investigated, but this research is one of the first to study the effects of stress on an immune organ – the spleen.

Any kind of stress can cause activation of the sympathetic nervous system. But the SNS’s direct effect on immune organs opens up new possibilities in the field of psychoneuroimmunology. It is only logical to wonder if other kinds of stressors can produce a change in cytokine expression. For example, can psychological stress or anxiety from daily life lead to sympathetic nervous system activation? If so, can this stress lead to changes in cytokine levels in the spleen or other immune organs such as thymus, lymph nodes, and gut? Answering questions like these can help us better understand how stressors interact with our ability to recover from an infection.

Additional Reference:

1.            Nicol, L. (1974). L’epopee pastorienne et la medicine veterinaire.  Pp 107-211.2.