Wichita Study of Cortisol and Interleukin 6

More than 10 years ago, the Centers for Disease Control and Prevention (CDC) began a surveillance study in Wichita, Kansas, that ended in 2002. This study served to identify people with CFS in the general population of Wichita and gave eligible subjects the opportunity to participate in a two-day clinical investigation.
 
A paper published in the April 2008 issue of Psychosomatic Medicine describes some of the results from this clinical study, focusing on what’s different about cortisol and interleukin 6 (IL-6) production in people with CFS versus people without fatigue
or people with general fatigue but not CFS.

Cortisol is a hormone that is synthesized in the adrenal glands. Interleukin 6 (IL-6) is an inflammatory cytokine, part of the immune system. Cortisol is important for modulating the immune response—especially inflammation. Once the inflammatory response has done its job, for example fighting off an infection, cortisol signals the immune cells to stop producing inflammatory molecules such as IL-6.

The authors note that this is the first study from a population-based sample to examine the diurnal rhythm of cortisol. Diurnal indicates a cycle that occurs every day. Cortisol levels are normally higher in the morning and decrease steadily throughout the day to the lowest point in the middle of the night. This diurnal rhythm of cortisol is critical for maintaining homeostasis, including a balanced immune response.

In this study investigators examined 28 people with CFS, 39 people with fatigue but insufficient symptoms to be diagnosed with CFS (ISF) and 39 people without fatigue (NF). To capture the diurnal rhythm of cortisol, saliva samples were collected from subjects from the time they woke to the time they retired for the evening. Only subjects with complete sets of saliva samples were included in the analysis (17 CFS, 23 ISF and 30 NF).

It’s also worth noting that the subjects were classified as CFS, ISF or NF based on measurement of impairment, fatigue and accompanying symptoms, rather than the 1994 CFS case definition.

The investigators found that both cortisol and IL-6 concentrations are different in people with CFS. The CFS subjects in the study had significantly lower cortisol levels throughout the day than did ISF and NF subjects. And IL-6 levels were slightly higher in the CFS subjects. The differences also appeared to be associated with more symptoms and increased symptom severity.

This study supports the extensive literature suspecting dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. It underscores the needs for serial measurements, particularly when assessing molecules that have well-characterized diurnal rhythm. The study also implicates cortisol and IL-6 in the severity of CFS symptoms.

Nater UM, Youngblood LS, Jones JF, Unger ER, Miller AH, Reeves WC, Heim C. Alterations in diurnal salivary cortisol rhythm in a population-based sample of cases with chronic fatigue syndrome. Psychosom Med 2008 Apr;70(3):298-305.

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