Ippei Kawano
One of the most fascinating reports from last year came from Charles Zucker's team regarding the interaction between the immune system and the brain. They discovered a set of neurons within the vagus nerve pathway that are triggered by peripheral inflammation. Silencing these neurons leads to uncontrolled and intensified inflammation, whereas activating them can reduce inflammation. This is a straightforward and elegant demonstration showing that the brain has the ability to regulate immune responses.
Why is it so interesting? Inflammation is a double-edged sword; it can protect the body from dangerous pathogens but can also cause significant damage if it is too intense. Most of the unpleasant symptoms associated with sickness, the lethargy, fever, pain, and swelling, are not the direct consequence of diseases but are rather caused by immune reactions against the pathogens. How does the body know how much immune activation is just right? Until now, immunologists mostly focused on communications between immune cells; there are immune cells that promote more inflammation, and there are others that suppress it. It is considered that the consensus emerges based on local interactions within the immune system. This paper, however, suggests that the information about immune activation is actually delivered to the brain, and the brain has the ability to tune the volume of the inflammatory response. It is tempting to speculate that the brain can integrate all the contextual elements (emotion, current state, future plan) to compute how intense the inflammation should be, and can finetune immune cell activity to fit its calculation.
This fits with a more recent understanding of the job of the brain — not to philosophize, not to create art or catharsis, not to love someone, but to regulate physiological parameters better. The brain integrates sensory information from outside (visual, auditory, olfactory, tactile, and taste) and from inside the body to create a model of what is most likely needed in the future and change physiological parameters preemptively to efficiently meet arising needs — a concept known as allostasis. Beyond the immune system, it is quite likely that other physiological regulations that were considered to be predominantly regulated at the organ level are also regulated by the brain, through a similar pathway. One candidate is whole-body energy expenditure. Later in 2024, Martin Picard and colleagues published a hypothesis that this brain regulation of body energy metabolism may be driving phenotypes of aging. How the same pathway may be dysregulated in obesity, anorexia, and cachexia is another interesting question.
How does the information about the inner environment reach the brain? As suggested by the paper, the journey starts from the vagus nerve whose branches are distributed all around the human body — it serves as a receptor of information about the current well-being of the organs. The vagus nerve reports to the nucleus tractus solitarius, from which it informs the monoamine system of the brain — serotoninergic, dopaminergic, noradrenergic, and cholinergic systems. These systems, therefore, may function like internal state reporters in the brain, like a gas meter. Monoamine projects to all over the brain to inform a summary version of the internal state of the body to the whole brain. Integrated information also reaches the insula; this part of the brain has also been reported to be activated by peripheral inflammation. The insula has connections to areas like the amygdala and nucleus accumbens, making this pathway relevant to emotion and behavior. This neuroanatomy suggests that this pathway may also be relevant to many psychiatric conditions.
