Two studies by Harvard Medical School and MIT start to demystify the complex link between brain and immune system, explaining how the latter may directly influence the areas of the brain that regulate emotions and social relationships. This discovery could change the future of treatment for neurological and psychiatric disorders.
After an infection or autoimmune disease flare-up, many people experience prolonged mood swings, persistent anxiety and changes in behaviour. Doctors have observed this phenomenon for decades, but until now it has been hard to unravel the precise connection between brain and immune system.
Now, two new studies by Harvard Medical School and Massachusetts Institute of Technology in Boston (United States) offer a detailed explanation.
Immune system and stress
The researchers have successfully mapped – step by step in laboratory animals – how the immune system influences specific areas of the brain responsible for emotions (such as anxiety and stress) and social behaviours, thus supporting brain activity. This paradigm shift could open the door to a different way of treating certain neurological and psychiatric disorders in the future.
“Identifying where and how cytokine receptors work in the brain, we have begun to unravel the complex relationship between the nervous and immune systems,” said Jun Huh, an immunologist at Harvard. "We hope these insights could eventually lead to new treatments for conditions like...anxiety.”
The pivotal role of cytokines
The researchers at Massachusetts Institute of Technology showed that two specific cytokines (IL-17A and IL-17C), produced by inflammatory mechanisms, increase the activity of the amygdala – the brain’s “fear centre”, which also processes emotions such as anxiety and stress. As we know, inflammation is one of the classic defence systems triggered by the immune system. A rise in these molecules makes mice more anxious, prompting them to avoid open spaces and reducing their ability to explore.
Conversely, another anti-inflammatory cytokine, IL-10, diminishes amygdala activity, with a “calming” effect on behaviour.
Therefore, the immune system produces substances that act by regulating mood, just as the classic neuromodulators (dopamine and endorphins) produced by the nervous system do to some extent.
The Harvard researchers, on the other hand, discovered that certain cytokines – IL-17A, IL-17B, IL-17E and IL-17F – enhance social behaviour in mice with autism-like traits. These animals normally show reduced social interest. However, when given a dose of cytokines, they become more engaged with other mice and also display fewer repetitive behaviours.
To the team’s surprise, it also found that one cytokine in particular (IL-17E) is produced by neurons within the brain itself, calling into question long-held beliefs – i.e. that cytokines were a product of the immune system – and opening up new avenues for research.
So what influences mood?
While new studies will be needed to understand whether the mechanisms published by the researchers also apply to humans, a new paradigm has emerged to determine which biological “pathways” really regulate our moods and emotional perceptions.
For centuries, people have believed that the “control centre” is almost exclusively in the brain, and most drug therapies have been designed based on this assumption. But connections with other systems (such as with the gut) are emerging more and more frequently, and now also with the immune system. In the future, some neurological and psychiatric disorders will likely be treated very differently from the way they are today (with drugs that regulate the immune response). Without doubt, the “cultural” approach will also need to change, which until now has led to rigid subdivisions of the body’s various systems (nervous system, immune system, and others). We are in fact a network of far more intricate and nuanced interactions.
