Unraveling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: The role of elastase, complement C4a and interleukin-1beta – Source: Journal of Internal Medicine, Apr 2010

[Note: complement C4a, which the study terms “a clinically important biomarker for postexertional malaise in people with ME/CFS,” is a protein encoded by the C4A gene, associated with the classical activation pathway, part of the immune system that can kill pathogens “without antibody participation.”]

Objectives: Too vigorous exercise or activity increase frequently triggers postexertional malaise in people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a primary characteristic evident in up to 95% of people with ME/CFS. The present study aimed at examining whether two different types of exercise results in changes in health status, circulating elastase activity, interleukin (IL)-1beta and complement C4a levels.

Design: Comparative experimental design.

Setting: University.

Subjects: Twenty-two women with ME/CFS and 22 healthy sedentary controls

Interventions: Participants were subjected to a submaximal exercise (day 8) and a self-paced, physiologically limited exercise (day 16). Each bout of exercise was preceded and followed by blood sampling, actigraphy and assessment of their health status.


• Both submaximal exercise and self-paced, physiologically limited exercise resulted in postexertional malaise in people with ME/CFS.

• However, neither exercise bout altered elastase activity, IL-1beta or complement C4a split product levels in people with ME/CFS or healthy sedentary control subjects (P > 0.05).

• Postexercise complement C4a level was identified as a clinically important biomarker for postexertional malaise in people with ME/CFS.


Submaximal exercise as well as self-paced, physiologically limited exercise triggers postexertional malaise in people with ME/CFS, but neither type of exercise alters acute circulating levels of IL-1beta, complement C4a split product or elastase activity.

Further studying of immune alterations in relation to postexertional malaise in people with ME/CFS using multiple measurement points postexercise is required.

Source: Journal of Internal Medicine, Apr 2010; 267(4):418-35. PMID: 20433584, by Nijs J, Van Oosterwijck J, Meeus M, Lambrecht L, Metzger K, Frémont M, Paul L. Department of Human Physiology, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium. Division of Musculoskeletal Physiotherapy, Department of Health Care Sciences, University College Antwerp;  Department of Physical Medicine and Physiotherapy, University Hospital Brussels;  Private Practice for Internal Medicine, Gent;  RED Laboratories N.V., Zellik, Belgium; Nursing and Health Care, Faculty of Medicine, University of Glasgow, Glasgow, UK. [Email: jo.nijs@vub.ac.be]

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