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Complement activation in a model of chronic fatigue syndrome.

Sorensen B, Streim JE, Strand M, Make B, Giclas PC, Fleshner M, Jones JF
Complement activation in a model of chronic fatigue syndrome
Journal of Allergy and Clinical Immunology 2003; 112:397-403.

Summary

The symptoms of CFS are similar to those seen in a systemic infection or in an inflammatory disease. Previous studies have attempted to identify alterations in immune function, levels of cytokines, and mediators of inflammation that could contribute to the pathogenesis of CFS. However, the frequency and type of the immune alterations vary from study to study, suggesting a need for a more focused approach. One approach is to observe patients in a situation known to induce an increase in symptoms. One such symptom trigger, also part of the CFS definition, is physical exertion; the other trigger known to reproduce symptoms of CFS is exposure to allergens. Both exercise and allergens also induce a variety of changes in physiologic function mimicking an infectious or inflammatory state.

This study serves as a model system of CFS in which patients and healthy subjects were challenged with an exercise or allergen stress. We measured pre- and post-challenge levels of illness symptoms, fatigue, cytokines, complement split products, and eosinophilic cationic protein. We hypothesized that challenge with either exercise or allergens would exacerbate the defining symptoms of CFS and induce the production of biological markers that correlated with an increase in these symptoms. The exercise challenge significantly exacerbated fatigue and generated reliable increases in the complement protein C4a. The increase in C4a was significantly correlated with post-exercise symptom scores. Further research concerning the biology of C4a is necessary to understand its role in the pathophysiology of CFS.

Abstract

Background: A need exists to identify biological markers in chronic fatigue syndrome (CFS).

Objective: To use an exercise and/or allergen challenge to induce the symptoms of CFS and to identify a biological marker that correlates with these symptoms.

Methods: Patients with CFS (n=32) and age-matched, normal control patients (n=29) exercised for 20 minutes on a stationary bike at 70% of their predicted maximum work load (Watts). Patients from each group with positive skin test results were also challenged with intranasally administered relevant allergens. Symptoms were recorded for 2 weeks before and 1 week after each challenge, using 3 different instruments. Blood samples were taken before, and 0, 1, 6, and 24 hours after challenges. Levels of complement split products, cell-associated cytokines, and eosinophilic cationic proteins were measured. Mean pre- and post-exercise symptom scores were evaluated for each group.

Results: Exercise challenge induced significant increases of the complement split products C4a, but not C3a or C5a, at 6 hours after exercise only in the CFS group (P<.01), regardless of allergy status. Mean symptom scores were significantly increased after exercise through the use of a daily diary (P<.03) and a weekly diary (P<.01) for the CFS group only. Mean scores for the Multidimensional Fatigue Inventory categories - reduced activity and mental fatigue - were significantly increased in the CFS group only (P<.04 and P<.02, respectively).

Conclusions: Exercise challenge may be a valuable tool in the development of diagnostic criteria and tests for CFS. Establishment of a role for complement activation products as markers for or participants in production of illness requires further study.

Page last modified on May 8, 2006

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