Researchers recently investigated the immune system's role in chronic fatigue syndrome in unprecedented depth. The findings might help design future treatments.

Chronic fatigue syndrome (CFS), or myalgic encephalomyelitis (ME), is a mysterious condition.

The main symptom of CFS is extreme and often unrelenting fatigue. Others include muscle and joint pain, sleep issues, and flu-like symptoms.

Researchers do not yet know what causes CFS. Suggestions include viral or bacterial infection, changes in the immune system, hormone imbalance, and mental health conditions.

Because of this, they have not yet been able to design a test that can diagnose CFS, and current treatments only relieve symptoms.

Over the years, interest in the role that the immune system might play in CFS has grown.

Often, people with CFS report that their symptoms began following an infection or other insult to the immune system. These reports are common, but once symptoms have appeared, it is impossible to assess how the body was behaving before they arrived.

Researchers from the Institute of Psychiatry, Psychology, and Neuroscience at King's College London in the UK used an interesting model to delve deeper.

Interferon-alpha

The researchers investigated people who were taking a treatment for hepatitis C called interferon-alpha. Interferon-alpha works by triggering the immune system in the same way that a significant infection would.

People who take this course of medication often report CFS-like symptoms during the treatment.

A smaller number of people go on to experience a CFS-like condition that can last 6 months after treatment has ended. The symptoms include fatigue, cognitive impairment, and joint and muscle aches.

The scientists followed 55 people who underwent this treatment. They assessed their fatigue levels and measured immune markers before interferon-alpha treatment began.

With this baseline information, they could monitor how each individual's immune system reacted to interferon-alpha.

Of the participants, 18 went on to develop CFS-like symptoms. The scientists have now published their findings in the journal Psychoneuroendocrinology.

Altered immune response

In those who went on to experience CFS-like symptoms, the researchers observed greater immune responses to the interferon-alpha treatment.

More specifically, this group produced around twice as much interleukin-10 and interleukin-6. Both of these molecules are important immune system messengers.

Those who went on to develop symptoms reported higher levels of fatigue during treatment, but they did not report higher levels of fatigue before treatment.

When investigating immune markers, the scientists saw that levels of interleukin-10 were elevated in these people before interferon-alpha treatment began. They also showed an exaggerated response to interleukin-10 and interleukin-6 early on in the treatment.

The team wonders whether this might mean that the immune system was already "primed" to over-respond.

"For the first time, we have shown that people who are prone to develop a CFS-like illness have an overactive immune system, both before and during a challenge to the immune system."

—Lead researcher Dr. Alice Russell

She goes on, "Our findings suggest that people who have an exaggerated immune response to a trigger may be more at risk of developing CFS."

Still much to learn

Interestingly, once the CFS-like illness developed, there were no longer any detectable differences between the immune systems of those who developed the symptoms and those who did not.

In another part of their study, the scientists compared the immune systems of 54 people with CFS with 57 people without CFS. Here, they found no significant differences in interleukin levels.

The researchers hope that these findings might open the future possibility of screening for people who might be most at risk of developing CFS. Of course, initially, it will be vital to replicate these results in people who develop CFS rather than a condition that mirrors CFS.

Because scientists do not yet fully understand CFS, any insight is crucial. The authors outline how they want to progress their understanding, saying:

"Future research will need to examine the molecular mechanisms that underlie an exaggerated immune response and that are involved in the conversion from acute to persistent fatigue symptoms."