Feeling sluggish, depressed, anxious, and having trouble concentrating while being sick might not just be due to physical weakness. Extensive reports from health professionals have pointed out that these symptoms, labeled "sickness behavior," are more than just side effects of the body fighting off an infection. They appear to be part of an intentional behavior pattern driven by a collaboration between the brain and the immune system.
This pattern may have evolutionary significance, helping to protect the community by reducing direct contact and preventing the spread of disease. Beyond that, it might hold valuable insights into mental health conditions, potentially leading to new treatment strategies.
Two studies from Harvard Medical School and the Massachusetts Institute of Technology (MIT), published in Cell, have brought us a step closer to understanding the molecular mechanisms behind how inflammation impacts our moods and behaviors. The research has identified which parts of the immune system communicate with the brain to explain this phenomenon.
Cytokines in Brain-Immune Crosstalk
Cytokines are small protein messengers released by a wide range of cells, especially immune cells. They help immune cells communicate, particularly when preparing to launch an inflammatory response to fight off pathogens.
Cytokines are not all the same; they fall into two broad categories: pro-inflammatory and anti-inflammatory, each playing a role in maintaining the delicate balance between fighting infections and preventing excessive inflammation.
To send messages, cytokines bind to receptors on their target immune cells, much like a key fitting into a lock, to fulfill their role in the immune system. Interestingly, cytokines don’t only affect immune responses; their impact extends to the brain, influencing cognition, mood, and behavior.
For example, a 2019 study on mice suggested that IL-17A, a cytokine released during fever caused by inflammatory infections, could explain the temporary reduction in social behavior often observed in autistic children. While this discovery hints at the complexity of brain-immune crosstalk, the full extent of it is still not well understood.
Read More: Visualizing Brain Connectivity May Aide in Diagnosing Mental Illnesses
Uncovering Cytokines’ Role in Mood and Behavior
The same researchers who conducted the cytokine study on autism expanded their research to investigate how and where cytokine signals in the brain affect mood, anxiety, and social behavior.
One study identified how specific cytokines, such as IL-17A and IL-17C, target the amygdala — the brain’s fear center — and influence its neural activity, leading to increased anxiety. Interestingly, when the researchers attempted to block the receptor (receptor antagonism is a common pharmacological effect of many commercial drugs), anxiety actually increased. Another fascinating finding was that the anti-inflammatory cytokine IL-10 seemed to reduce anxiety.
Another study further explored cytokines’ role in mood regulation by returning to autism-like behaviors. It identified several cytokines and their receptors, in addition to IL-17A, that appear to enhance social interactions in mice with autism-like traits. Notably, IL-17E was also found to be produced by neurons in the brain, positioning it as a neuromodulator, much like other neurotransmitters such as serotonin and dopamine.
"Our results emphasize the important role of immune signaling in shaping mood and behavior by acting on specific brain pathways," explained co-senior author Gloria Choi, Associate Professor at MIT’s Picower Institute for Learning and Memory, in a press release.
Potential Alternatives to Traditional Psychiatric Drugs
"By identifying where and how cytokine receptors work in the brain, we have begun to unravel the complex relationship between the nervous and immune systems in the effect of this complex crosstalk on mood and behavior,” said Jun Huh, associate professor of immunology in the Blavatnik Institute at HMS and co-senior author on the two studies in the press release.
While Huh’s and Choi’s research brings us forward in understanding brain-immune communication, more studies are necessary, especially regarding human application.
In the future, new treatments for autism and anxiety disorders could be a result of these initial findings. Unlike traditional psychiatric drugs, which alter brain chemistry directly, these therapies may adjust immune signals from outside the brain, offering a novel approach using the immune system.
Read More: Excessive Worry About Health Could be Signs of Illness Anxiety Disorder
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Having worked as a biomedical research assistant in labs across three countries, Jenny excels at translating complex scientific concepts – ranging from medical breakthroughs and pharmacological discoveries to the latest in nutrition – into engaging, accessible content. Her interests extend to topics such as human evolution, psychology, and quirky animal stories. When she’s not immersed in a popular science book, you’ll find her catching waves or cruising around Vancouver Island on her longboard.
