title: Acute phase responses and cytokine secretion in chronic fatigue syndrome.
abstract: 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-1beta (IL-1beta) 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 alpha2-macroglobulin were 29% higher in CFS patients (P < 0.008) compared to controls. Secretion of IL-6 was generally higher for CFS patients (approximately 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 alpha2-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-1beta secretion by cells from healthy control subjects (R = 0.603, P = 0.022), but not from CFS patients, and IL-1beta 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 alpha2-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 alpha2-macroglobulin concentrations. These modest differences suggest that cytokine dysregulation is not a singular or dominant factor in the pathogenesis of CFS.
authors.affiliation: Department of Medicine, New England Medical Center, Boston, Massachusetts 02111, USA. jgc2@psu.edu
authors.forename: J G
authors.initials: JG
authors.lastname: Cannon
authors.forename: J B
authors.initials: JB
authors.lastname: Angel
authors.forename: R W
authors.initials: RW
authors.lastname: Ball
authors.forename: L W
authors.initials: LW
authors.lastname: Abad
authors.forename: L
authors.initials: L
authors.lastname: Fagioli
authors.forename: A L
authors.initials: AL
authors.lastname: Komaroff
mesh_terms: D000210:Acute-Phase Reaction; D001831:Body Temperature; D016207:Cytokines / Q000378:metabolism*; D015444:Exercise; D015673:Fatigue Syndrome, Chronic / Q000276:immunology*; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D000511:alpha-Macroglobulins / Q000032:analysis
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D000511:alpha-Macroglobulins