Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome

J Rheumatol. 1997 Feb;24(2):372-6.


Objective: Chronic fatigue syndrome (CFS) has been hypothesized to result from immune activation. We examined the role of serum markers of inflammation and immune activation among patients with CFS and in those with chronic fatigue (CF) not meeting the case definition.

Methods: Assays for soluble interleukin 2 (IL-2) receptor, IL-6, C-reactive protein, beta 2-microglobulin, and neopterin were performed in 153 fatigued patients in a referral clinic. Patients were classified according to whether they met criteria for CFS, reported onset of illness with a viral syndrome or had a temperature > 37.5 degrees C on examination.

Results: Compared to control subjects, mean concentrations of C-reactive protein, beta 2-microglobulin, and neopterin were higher in patients with CFS (p < or = 0.01) and CF (p < or = 0.01). Results did not distinguish CFS from CF. IL-6 was elevated among febrile patients compared to those without this finding (p < or = 0.001), but other consistent differences between patient subgroups were not observed. The presence of several markers was highly correlated (p < 0.01).

Conclusion: Our findings that levels of several markers were significantly correlated points to a subset of patients with immune system activation. Whether this phenomenon reflects an intercurrent, transient, common condition, such as an upper respiratory infection, or is the result of an ongoing illness associated process is unknown. Overall, serum markers of inflammation and immune activation are of limited diagnostic usefulness in the evaluation of patients with CSF and CF.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Biomarkers / analysis*
  • Biopterin / analogs & derivatives
  • Biopterin / blood
  • C-Reactive Protein / metabolism
  • Chronic Disease
  • Diagnosis, Differential
  • Enzyme-Linked Immunosorbent Assay
  • Fatigue / diagnosis
  • Fatigue / immunology*
  • Fatigue / metabolism
  • Fatigue Syndrome, Chronic / diagnosis
  • Fatigue Syndrome, Chronic / immunology*
  • Fatigue Syndrome, Chronic / metabolism
  • Female
  • Humans
  • Immunity
  • Interleukin-6 / blood
  • Male
  • Neopterin
  • Receptors, Interleukin-2 / blood
  • beta 2-Microglobulin / metabolism


  • Biomarkers
  • Interleukin-6
  • Receptors, Interleukin-2
  • beta 2-Microglobulin
  • Biopterin
  • Neopterin
  • C-Reactive Protein