Chronic fatigue syndrome: intracellular immune deregulations as a
possible etiology for abnormal exercise response.

Med Hypotheses. 2004;62(5):759-65.

Jo Nijs [*, a, b], Kenny De Meirleir [a, c], Mira Meeus [a],
Neil R. McGregor [d, e] and Patrick Englebienne [f, g]

Affiliations:
[a] Department of Human Physiology, Faculty of Physical Education and
Physical Therapy Science, Vrije Universiteit Brussel (VUB), Brussel 1090,
Belgium
[b] Institute for Occupational and Physical Therapy, Department of Health
Sciences, Hogeschool Antwerpen, Belgium
[c] Chronic Fatigue Clinic, Vrije Universiteit Brussel (VUB), Belgium
[d] Bio21, Institute of Biomedical Research, University of Melbourne,
Parksville, Victoria 3000, Australia
[e] Dental Clinical School, Westmead Hospital, Westmead, Australia
[f] Department of Nuclear Medicine, Université Libre de Bruxelles (ULB),
Belgium
[g] RED Laboratories N.V., Zellik, Belgium

[*] Corresponding author. Present address: Vakgroep
MFYS/Sportgeneeskunde, AZ-VUB KRO gebouw 1, Laarbeeklaan 101, 1090
Brussel, Belgium. Tel.: +32-2-477-4604; fax: +32-2-477-4607 E-Mail:
mailto:jo.nijs@vub.ac.be

Received 1 October 2003;  accepted 9 November 2003.  Available online 20
February 2004.


The exacerbation of symptoms after exercise differentiates Chronic
fatigue syndrome (CFS) from several other fatigue-associated disorders.
Research data point to an abnormal response to exercise in patients with
CFS compared to healthy sedentary controls, and to an increasing amount
of evidence pointing to severe intracellular immune deregulations in CFS
patients.

This manuscript explores the hypothetical interactions between these two
separately reported observations. First, it is explained that the
deregulation of the 2-5A synthetase/RNase L pathway may be related to a
channelopathy, capable of initiating both intracellular hypomagnesaemia
in skeletal muscles and transient hypoglycemia. This might explain muscle
weakness and the reduction of maximal oxygen uptake, as typically seen in
CFS patients.

Second, the activation of the protein kinase R enzyme, a characteristic
feature in at least subsets of CFS patients, might account for the
observed excessive nitric oxide (NO) production in patients with CFS.
Elevated NO is known to induce vasidilation, which may limit CFS patients
to increase blood flow during exercise, and may even cause and enhance
postexercise hypotension.

Finally, it is explored how several types of infections, frequently
identified in CFS patients, fit into these hypothetical
pathophysiological interactions.

Copyright © 2004 Elsevier Ltd. All rights reserved.