How Inflammation Affects Mood and Behavior in Systemic Autoinflammatory Diseases

inflammation and behaviorMany questions have been asked about behavior issues, and if there is a connection with autoinflammatory syndromes, especially with younger kids who can get moody and even aggressive in a flare and have a hard time explaining their emotions. There is research on how inflammation causes “sickness behavior syndrome.” While the research is not specific to autoinflammatory illnesses, the inflammatory cytokines studied are the same ones that are involved in the various autoinflammatory diseases.

The “gist” of the studies are that pro-inflammatory cytokine markers get into the brain and do affect behavior and mood. And it’s not just humans who experience sickness behavior. These mood changes and behaviors can be found in all mammals and birds reports the authors of Twenty Years of Research on Cytokine-Induced Sickness Behavior published in the journal Brain Behavior and Immunity. This behavioral adaptation is thought to protect other members of the community from disease by making the sick members feel the need to separate from the group.

These are symptoms noted in a variety of conditions in general. It would be good to have more research on this specifically for autoinflammatory diseases.

Sickness Behavior Symptoms:

  • Anhedonia (emotional numbness)
  • Depressed Mood
  • Cognitive Dysfunction
  • Loss of Social Interest
  • Fatigue
  • Low Libido
  • Poor Appetite
  • Somnolence
  • Sensitivity to Pain (Patients tell us these syndromes are very painful – read more here.)
  • Malaise
  • Anxiety
  • Inability to Concentrate

Targeting Inflammation to Treat Depression

In this video, Dr. Miller of Emory University discusses how inflammation can affect the brain and cause depression. He also discusses how a study led by researchers at Emory University showed that in patients who had depression and high inflammatory markers, using a biologic medication that targeted tumor necrosis factor (TNF), improved the depression symptoms. TNF is also involved in many autoinflammatory diseases, and for some the treatment is a biologic that targets this inflammatory cytokine.

CBSM Effects on Sickness Behavior and Pro-Inflammatory Cytokine Mechanisms in Breast Cancer Survivors

This dissertation, written by Orit Birnbaum-Weitzman of the University of Miami, looked at sickness behavior in breast cancer patients. It was determined that sickness behavior symptoms were associated with IL-6 and TNF-alpha. It was also found that the higher the levels of TNF-alpha, the longer it took the physical sickness symptoms to disappear.

Interestingly, these are some of the same inflammatory cytokines that are also known to be overproduced in several periodic fever syndromes, including Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) and Familial Mediterranean Fever (FMF).

How Inflammatory Disease Causes Fatigue

This 2009 study published in The Journal of Neuroscience reports that, “behavioral changes suffered by those with chronic inflammatory diseases are caused by the infiltration of immune cells into the brain.” The study looked at mice with inflamed livers. In these mice, monocytes, a type of white blood cell, were found in the brain. When researchers blocked chemicals in the brain that were allowing the monocytes into the brain, sickness behavior was reduced in the mice.  Leukocytosis, a condition where the total white blood count (WBC), including monocytes are elevated, is a common finding in many systemic autoinflammatory diseases.

fever syndrome behaviorIs Your Immune System Making You Cranky? UA Studies Inflammation, Behavior – University of Arizona Report

While it has been known for decades that chronically ill patients tend to suffer from sickness behaviors such as depression, it’s becoming more recognized that it’s not just the stress of the illness that is the cause. Dr. Charles Raison of the University of Arizona College of Medicine reports that,When the body is sick, it produces inflammatory chemicals, called cytokines, as part of the natural immune response to illness. Those chemicals can essentially “commandeer the brain” and make a person feel depressed…”

Mood as a Symptom of Autoinflammatory Diseases

With autoinflammatory conditions in particular, the sickness behavior can seem to make a person, especially young kids, appear moody and unpredictable. This especially true in the conditions that have distinct periods of illness, or flares, and then periods of health where the person has few if any symptoms of their disease. As the fever, rash, and mouth ulcers fade away, often so does the sickness behavior. The sickness behavior can also follow the same course as the disease, coming and going unpredictably for some patients.

Understand that mood changes can be part of the autoinflammatory condition your loved one battles. Not only does the systemic inflammation cause mood changes, these diseases are extremely painful as patients describe here. Just as anyone would not be in the best of moods with a bad flu or severe painful injury, patients whose symptoms are flaring will have mood changes, especially young kids. For young kids who know no other way to communicate their pain and feelings of illness than with frustration or anger, it can be beneficial to consult with a therapist on how to best help your child learn to better communicate how they feel during a flare.

It is important to note behavior or mood changes that you notice in yourself, or a loved one that may be having these issues, along with any autoinflamatory disease symptoms on a daily log or calendar.  Take this information to your doctor, and ask them for advice on how to have these symptoms evaluated and managed.

Ideally, with good treatment of the disease that reduces the systemic inflammation, the sickness behavior should decrease, just as you may see other symptoms, such as rash, fever, and joint pain decrease with successful treatment.

Seek immediate professional help if there are serious concerns, such as any alterations in cognitive abilities, speech,  motor functioning, instability, or signs that the patient wants to harm themselves, or others.

 The Autoinflammatory Alliance is a nonprofit organization dedicated to helping those with autoinflammatory diseases.

Donate now to help with awareness, education, and research for these rare diseases.


  1. Scholarly Repository: CBSM Effects on Sickness Behavior and Pro-Inflammatory Cytokine Mechanisms in Breast Cancer Survivors
  2. Science Daily: How Inflammatory Disease Causes Fatigue
  3. UA News: Is Your Immune System Making You Cranky? UA Studies Inflammation, Behavior
  4. Profile of blood cells and inflammatory mediators in periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome
  5. Periodic Fever Syndromes, Paul R. School, MD
  6. Brain Behavior and Immunity: Twenty Years of Research on Cytokine-Induced Sickness Behavior
  7. NIH: Cytokine, Sickness Behavior, and Depression
  8. BMC Medicine: Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways
  9. FJPsych Advances: Inflammation and its relevance to psychiatry
  10. Emory: Targeting inflammatory to treat depression


*Top photo by Martha Tousseau

*Bat photo by Zeusandhera, Flickr

Updated 10/2017

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