Journal of Clinical Immunology

, Volume 19, Issue 6, pp 414-421

First online:

Acute Phase Responses and Cytokine Secretion in Chronic Fatigue Syndrome

  • Joseph G. CannonAffiliated withDepartment of Medicine, New England Medical CenterNoll Physiological Research Center, Pennsylvania State University Email author 
  • , Jonathan B. AngelAffiliated withDepartment of Medicine, New England Medical Center
  • , Richard W. BallAffiliated withNoll Physiological Research Center, Pennsylvania State University
  • , Leslie W. AbadAffiliated withNoll Laboratory, Pennsylvania State University
  • , Laura FagioliAffiliated withUSDA Jean Mayer Human Nutrition Research Center on Aging, Tufts University
  • , Anthony L. KomaroffAffiliated withUSDA Jean Mayer Human Nutrition Research Center on Aging, Tufts University

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This study addresses the hypothesis that clinical manifestations of chronic fatigue syndrome (CFS) are due in part to abnormal production of or sensitivity to cytokines such as interleukin-1β (IL-1β) and IL-6 under basal conditions or in response to a particular physical stress: 15 min of exercise consisting of stepping up and down on a platform adjusted to the height of the patella. The study involved 10 CFS patients and 11 age-, sex-, and activity-matched controls: of these, 6 patients and 4 controls were tested in both the follicular and the luteal phases of the menstrual cycle, and the remainder were tested in only one phase, for a total of 31 experimental sessions. Prior to exercise, plasma concentrations of the acute phase reactant α2-macroglobulin were 29% higher in CFS patients (P < 0.008) compared to controls. Secretion of IL-6 was generally higher for CFS patients (~38%), however, this difference was statistically significant only if all values over a 3-day period were analyzed by repeated-measures ANOVA (P = 0.035). IL-6 secretion correlated with plasma α2-macroglobulin in control subjects at rest (R = 0.767, P = 0.001). Immediately after exercise, the CFS patients reported greater ratings of perceived exertion (P=0.027) compared to the healthy control subjects. Ratings of perceived exertion correlated with IL-1β secretion by cells from healthy control subjects (R = 0.603, P = 0.022), but not from CFS patients, and IL-1β secretion was not different between groups. Exercise induced a slight (<12%) but significant (P = 0.006) increase in IL-6 secretion, but the responses of the CFS patients were not different than controls. Furthermore, no significant exercise-induced changes in body temperature or plasma α2-macroglobulin were observed. These data indicate that under basal conditions, CFS is associated with increased IL-6 secretion which is manifested by chronically elevated plasma α2-macroglobulin concentrations. These modest differences suggest that cytokine dysregulation is not a singular or dominant factor in the pathogenesis of CFS.

Chronic fatigue syndrome acute phase responses