Our immune system is a powerful force inside each one of us! This protective system is charged with the job of responding to foreign invaders to keep us in optimal health. Most of us do not think too much about this system until it is not working correctly.
I treat many patients that suffer from overactive or under-active immune systems due to chronic infections, like tick-borne diseases; toxic exposures, like mold and mycotoxins; or autoimmune diseases, like multiple sclerosis, lupus or Hashimoto’s thyroiditis. Although many patients understand the important role of the immune system in protection and defense, few people know that it also controls our behavior.
A recent study discussed the role of cytokines activated when the immune system goes on red alert and the connection to social isolation and autistic behaviors. It is even plausible that changes in immune function may lead to personality changes!
Interferon-Gamma: A Key Immune Signal
One of the key molecules is interferon-gamma (IFN-gamma) secreted by activated white blood cells of the immune system. Once this molecule crosses into the brain, it inhibits the neurons in the pre-frontal cortex. If the pre-frontal cortex is inhibited, the patient actually becomes more social. So if the immune system is activated, a person may feel more social.
However, in a patient with an immune deficiency, we may see the opposite effect, more isolation and antisocial behavior. This new data suggests that an impaired immune system may contribute to numerous neuro-psychiatric conditions. It may contribute to isolation or depression when someone is sick and the immune system is not functioning properly.
As we learn more, it may help us to understand the difficulties faced by those with immune dysfunction due to chronic infection or toxic mold exposure. It may even lead to changes in the relationships to people closest to us, such as our friends, children and spouse, if they do not understand the effect of the illness on your decreased desire for social interactions.
Inflammatory Cytokines And The Brain
A recent article about inflammatory cytokines and brain signaling discussed inflammation and the brain:
When considering the pathological signaling cascades in immunological disorders of the brain, certain cytokines might be considered of key importance, with their presence determining the course of a particular disease. Interleukin-1 (IL-1), IL-6, IL-17, and TNFα are critical for the pathogenesis of inflammation in certain brain disorders. Targeting these cytokines or their receptors can alter the course of several neurological diseases, but the effects may be beneficial or harmful.
We understand from this article that the inflammatory signals of the immune system (cytokines) have a profound effect on the brain. Many patients battling systemic inflammatory or autoimmune disorders suffer from an “inflamed brain” and all that goes with it, symptoms like depression, anxiety, and insomnia.
The role of cytokines on behavior can be summarized by saying that TNFα (sickness and depression) and IL-1β (sickness), alter behavior by direct actions on neurons of the brain.
GABA Affects The Immune System Too
GABA, an inhibitory neurotransmitter in the brain, has a similar inhibitory effect on the immune system. Antigen Presenting Cells (APCs) of the immune system have GABA receptors and therefore, GABA can directly inhibit the function of these immune cells. What this means is, this neurotransmitter from the brain may have a direct inhibitory effect on the body’s immune system.
An article on GABA and the immune system states:
“Intricate and reciprocal regulatory relationships exist between the nervous system and the immune system, mediated in part by chemical messengers, like GABA. This has been clearly demonstrated for the central nervous system through the hypothalamic–pituitary–adrenal axis”
Insults to the body, from the outside or from the inside, activate the cells of the innate immune system. The immune response transmits this information to the brain to cause physiological and behavioral responses.
A mild inflammatory response – such as a low-grade infection, trauma (such as dropping a weight on one’s foot) or even strenuous exercise – results in reversible consequences, as they are a result of altered cellular (neuron) function.
A severe response induces often irreversible consequences as a result of cell death. In either case, the causal event is initiated by monocytic and dendritic cells with the initiation of an inflammatory response1.
Sickness and Depression
Perhaps no connection has been more studied than that of immune activation and inflammation and the link to depression. Systemic infections cause the patient to allocate limited resources, conserve energy and prevent spread of infection. The resulting sickness behavior is common to most infections, including viruses, bacteria and multi-cellular parasitic infections.
There is a broad spectrum of symptoms – fever, nausea, decreased appetite, malaise, fatigue and achiness – all of which may aid in the fight to conserve resources and increase isolation-type behavior.
In animal models we see sickness associated with a decrease in time seeking interaction with other animals, as a result of diminished motivation for social exploration. Symptoms of depression appear after pro-inflammatory cytokines are produced by the body or if they are administered experimentally.
The fact that inflammation often leads to later depression suggests a cause–effect relationship. It indicates that immune activation can precipitate depression. Many symptoms of inflammation-induced depression overlap with sickness behaviors, including fatigue, changes in sleep pattern, lack of interest in daily or pleasurable activities (anhedonia), changes in appetite or body mass, and unexplained aches and pains
The Journal of Experimental Biology Article concludes
- Independent of the type of infection, the inflammatory response may cause behavioral changes.
- Pro-inflammatory cytokine expression is a precursor for behavioral changes.
- Behavior is controlled by neuronal function. Behavioral changes associated with infection are a result of inflammatory cytokine interaction with neurons.
So perhaps we should dig deeper if we or a loved one is experiencing depression and finding less pleasure in social activities. It is quite possible that hidden infection or an inflammatory condition may be the cause of the personality changes. Bottom line is to have compassion, there is more to it than meets the eye!
|↑1||McCusker, Robert H., and Keith W. Kelley. “Immune–neural connections: how the immune system’s response to infectious agents influences behavior.” Journal of Experimental Biology 216, no. 1 (2013): 84-98.|