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Chronic Fatigue Syndrome > Publications > Pathophysiology >

Association of peripheral inflammatory markers with chronic fatigue in a population-based sample.

Raison CL, Lin JS, Reeves WC.
Brain Behavior and Immunity. DOI: 10.1016/j.bbi.2008.11.005.

Summary

There has been considerable debate over the years concerning the role the immune system plays in the pathophysiology of CFS. Previous studies have been confounded by factors such as small numbers of patients, recruiting patients from tertiary care clinics, inappropriate or no controls, non-standardized diagnostic criteria, and failure to control for comorbid medical and psychiatric conditions that are also associated with inflammation. C-reactive protein (CRP) provides one measure of innate immune system activity and white blood cell count (WBC) is another general measure of inflammation. This study measured high-sensitivity CRP, WBC, and a combined inflammation factor in 102 individuals with CFS, 240 unwell people not meeting criteria for CFS, and 115 well controls. Participants were randomly recruited from metropolitan, urban, and rural communities in Georgia, obviating bias associated with clinical referral studies. Controls were also selected from the community and we used recommended standardized and validated instruments to diagnose CFS. Finally, we carefully assessed participants for comorbid medical and psychiatric conditions and medication use. We found that persons with CFS had significantly higher levels of CRP than did well individuals and also had higher scores on an inflammatory factor that included both CRP and WBC count. However, unwell participants not meeting criteria for CFS had similar levels of inflammation as those with CFS. Inflammation was also associated with depressive symptoms, weight, and being a woman. Finally, we found a strong association between inflammation and disability from physical symptoms but not with disability associated with mental symptoms such as anxiety. The findings would indicate that people with increased inflammation – from whatever source – are more likely than others to develop symptoms (e.g., fatigue, pain, disturbed sleep, and troubles with thinking and memory) that frequently lead to a diagnosis of conditions such as CFS. Because even mild increases in inflammatory markers like CRP have been shown to predict the later development of many serious illnesses, providers should consider this in their management plan for CFS patients.

Abstract

Alterations in the innate immune response may contribute to the pathogenesis of chronic fatigue syndrome (CFS). However, studies have been limited by small sample sizes, use of patients from tertiary care settings, inappropriate selection of controls, and failure to control for confounding demographic, medical and behavioral factors independently associated with immune activity. It is also not known whether specific symptoms account for observed associations between CFS and the innate immune response. To address these limitations, the current study examined plasma concentrations of high-sensitivity c-reactive protein (hs-CRP), white blood cell count (WBC) and a combined inflammation factor in a large population-based sample. Log transformed mean plasma concentrations of hs-CRP were increased in subjects with CFS (n=102) and in subjects with unwellness symptoms that did not meet diagnostic criteria for CFS (defined as "insufficient fatigue" [ISF]) (n=240) when compared to subjects who were well (n=115). Log transformed WBC was increased in ISF and was increased at a trend level in CFS. The combined inflammation factor was increased in both CFS and ISF. Subjects with CFS and ISF did not differ on any of the inflammation measures. In the entire subject population, the physical component summary score (PCS), but not the mental component summary score (MCS), from the Medical Outcomes Study Short Form-36 (SF-36) was negatively associated with each of the inflammation measures. Depressive symptoms were also associated with increased log hs-CRP. After adjustment for age, sex, race, location of residence, BMI, depressive status and immune modulating medications, subjects classified as ISF continued to demonstrate increased log hs-CRP, WBC and elevations on the inflammation factor when compared to well controls; however, associations between CFS and log hs-CRP and the inflammation factor were no longer statistically significant. After adjustment, PCS score also remained independently associated each of the inflammation measures. These findings support a role for innate immune activation in unexplained fatigue and unwellness, but do not suggest that immune activation is specific to CFS.

Page last modified on January 15, 2009

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