Chronic Allergic Inflammation's Impact on Brain Chemistry and Mood: Gary Falcetano, PA-C, AE-C

Gary Falcetano, PA-C, AE-C

Chronic allergic inflammation affects brain chemistry and mood regulation through cytokine dysregulation, increased blood-brain barrier permeability, and neurotransmitter system interference, Gary Falcetano, PA-C, AE-C, US Scientific Affairs Manager for Allergy at Thermo Fisher Scientific, detailed in an interview with The American Journal of Managed Care® (AJMC®).

Falcetano also highlighted 3 specific brain regions significantly impacted by inflammation, influencing emotional well-being, which include the hippocampus, prefrontal cortex, and amygdala. Finally, he added that chronic inflammation can dysregulate the hypothalamic-pituitary-adrenal axis, leading to altered cortisol levels, which further affects mood and cognition.

This transcript was lightly edited for clarity.

Transcript

AJMC: Can you elaborate on the specific mechanisms by which chronic allergic inflammation can affect brain chemistry and subsequently influence mood regulation? Explain how the dysregulation of specific cytokines in allergic individuals might directly interfere with neurotransmitter systems, such as serotonin production.

Falcetano: I think with chronic allergic inflammation, it can really affect brain chemistry and mood regulation through several mechanisms, primarily involving cytokine dysregulation, blood-brain barrier (BBB) permeability, and neurotransmitter system interference. Let's break these down individually.

We know that chronic allergic inflammation involves the dysregulation of cytokines, like interleukins IL-4/IL-5/IL-13, tumor necrosis factor (TNF)-α, interferon (IFN)-γ. All of these are crucial in mediating allergic responses and inflammation. The issue is, if these get into the brain, we start to see effects on the brain tissue.

How do they get into the brain? That's through that second point, an increase in blood-brain barrier permeability that allows these cytokines, other inflammatory mediators, to enter the brain, leading to a certain degree of neuroinflammation.

If we look at the neurotransmitters, for instance, serotonin and dopamine, we know that cytokines, like IFN-γ and TNF-α, activate the kynurenine pathway. The kynurenine pathway actually depletes tryptophan, which is a primary amino acid precursor of serotonin. We know it plays a significant role in both regulating mood and emotional well-being, so having that disrupted through that pathway can be a real issue with inflammation from this.

When we move over to the dopamine system, those proinflammatory cytokines affect the dopamine synthesis by influencing the activity of enzymes that are involved in its production. They also actually impair the function of the dopaminergic neurons, which are critical to mood regulation, motivation, and pleasure centers. That's the neurotransmitter side, but if we look at those specific areas in the brain that are affected, there are 3 main areas that are affected that really play into emotional well-being.

We know that the hippocampus is basically essential for converting short-term memories into long-term memories. It helps organize and store new information, including factual memories, emotional associations with memories, and even spatial navigation, which may explain why, personally, my internal autopilot while driving seems off when I’m suffering from my seasonal allergies.

In another area of the brain, the prefrontal cortex, we see that inflammation can impair function, which involves executive function and emotional regulation. Anybody with a teenager in the house knows that not having a completely developed prefrontal cortex can affect our behaviors, your personality, and social appropriateness.

Finally, the amygdala: having inflammation there can actually cause an increase in anxiety and stress responses. They all can impact our definite emotional stability and well-being. When we have chronic inflammation, it can dysregulate the hypothalamic-pituitary-adrenal axis, leading to altered cortisol levels, which can also certainly affect mood and cognition.