Tired But Overactive?
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By Damaris Christensen

Tired But Overactive?

Immune system activity is linked to cancer fatigue

By Damaris Christensen


For some cancer survivors, getting out of bed, carrying groceries or simply walking a block can be exhausting even weeks or years after treatment. A study in the May 1 issue of Clinical Cancer Research now links the draining lassitude of persistent fatigue—which affects up to 30 percent of breast cancer survivors—to an overactive immune system.

“This [fatigue] is not depression … and it is not stress,” says Michael R. Irwin, a psychiatrist at the Cousins Center for Psychoneuroimmunology at the University of California at Los Angeles (UCLA), and the study’s senior author. “There’s a biologic basis for the fatigue symptoms.”

Currently, there is no diagnostic test for persistent fatigue. However, in their laboratory, Irwin and his colleagues could accurately distinguish which cancer survivors experienced persistent fatigue by evaluating the amount of two proteins on a woman’s immune cells. Analysis of these indicators, called biomarkers, correctly categorized 87 percent of the 50 women in the study—32 of whom suffered from fatigue and 18 of whom did not. All of the women had completed treatment for breast cancer at least a year before the study started.

Biomarkers could significantly aid research aimed at understanding persistent fatigue, notes Kevin Zbuk, a clinical fellow at the Genomic Medicine Institute at the Cleveland Clinic Foundation, who was not involved in the research. Biomarkers could provide a “very useful companion” to more subjective fatigue scales that are based on questionnaires, he says.

Irwin and his colleagues assessed their first biomarker by measuring a protein called the IL-6 receptor, which is usually found on the surface of white blood cells named monocytes. However, as the immune system is activated, the monocytes shed the IL-6 receptors into the bloodstream. There, the proteins interact with other cells such as brain cells that may regulate feelings of fatigue, Irwin speculates. The more IL-6 receptors that the scientists found dissolved in blood plasma, compared to the amount they found on cells, the greater the likelihood a woman had fatigue.

The second biomarker the researchers evaluated was a type of immune cell sporting a protein called CD69 on its surface. Women with persistent fatigue tended to have lower numbers of immune cells carrying CD69 proteins, the researchers noted.

“It’s too early to make a link to patient outcomes,” cautions Zbuk, who notes, as does Irwin, that this relatively small study needs to be confirmed in larger prospective trials. However, Zbuk says, “this study provides a very interesting physiologic perspective” from which to study and monitor persistent fatigue.

Irwin and his colleagues at UCLA are now in the early stages of investigating a drug that blocks an overactive immune response, hoping that it shows potential as a treatment for persistent fatigue.  CR endbox