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kan bij ontregeling

van het afweersysteem

de gezondheid schaden.






De inflammatoire reaktie van het afweersysteem als gevolg van inspanning kan,

volgens Cooper en kollega's, in bepaalde medische situaties de gezondheid schaden.


De kern van hun verhaal laat zich als volgt samenvatten:

inspanning leidt (ook bij gezonde mensen) tot een inflammatoire response (IL-6, NO etc.)

als leukocyten (witte bloedcellen) vooraf (chronisch) geprikkeld zijn

(bijv. als gevolg van infecties, verwondingen of luchtverontreiniging),

leidt inspanning er toe dat inspanning (per saldo) negatief uitpakt.




Opvallende vaststellingen in het studierapport zijn voorts dat

  • fysiologische stress een (veel) sterkere inflammatoire response tot stand lijkt te brengen (klik hier) dan psychologische stress (klik hier en hier), en
  • fysieke stress het "leaky gut"-fenomeen kan doen veroorzaken, waardoor darmbacteriŽn de bloedbaan bereiken en een inflammatoire response veroorzaken (klik hier of hier).

Opmerkelijk is voorts het raakvlak met een grote groep ME/CVS-patiŽnten (klik hier en hier).




Dangerous exercise: lessons learned from dysregulated inflammatory responses to...

Numerous exercise abnormalities been found in Chronic Fatigue Syndrome (CFS)

11 March 2010


Tom Kindlon,

Information Officer (voluntary position)

Irish ME/CFS Association

One curious omission from this interesting review [1] is Chronic Fatigue Syndrome (CFS), which is also sometimes known as Myalgic Encephalomyelitis (ME). An abnormal response to physical activity is an essential part of widely used ME/CFS clinical criteria for adults [2] and children [3]. The most frequently used research criteria for CFS [4] require that patients, along with suffering from chronic debilitating fatigue lasting at least 6 months, have at least 4 out of a list of 8 symptoms, one of which is "postexertional malaise lasting more than 24 hours."


There is a growing body of research on abnormal responses to exercise in CFS. A recent review [5] covers the issue in a fairly comprehensive manner - here's a summary:


"Exertion induces post-exertional malaise with a decreased physical performance/aerobic capacity, increased muscoskeletal pain, neurocognitive impairment, "fatigue", and weakness, and a long lasting "recovery" time.


This can be explained by findings that exertion may amplify pre-existing pathophysiological abnormalities underpinning ME/CFS, such as inflammation, immune dysfunction, oxidative and nitrosative stress, channelopathy, defective stress response mechanisms and a hypoactive hypothalamic-pituitary-adrenal axis."


High rates of adverse reactions to graded exercise programs have been reported in patients with CFS Ė sometimes 50% or greater [6].


CFS remains a fairly poorly understood condition.

There is increasing evidence that CFS is heterogeneous and this heterogeneity could be of relevance t therapeutic programs involving exercise [7,8]. Those interested in researching abnormal responses to physical activity, including dysregulated inflammatory responses, could find much of interest if they chose to study CFS.





1) Cooper DM, Radom-Aizik S, Schwindt C, Zaldivar F Jr. Dangerous exercise: lessons learned from dysregulated inflammatory responses to physical activity. J Appl Physiol. 2007 Aug;103(2):700-9. Epub 2007 May 10.

2) Carruthers BM, Jain AK, De Meirleir KL, Petersn DL, Klimas MD, Lerner AM, Bested AC, Flor-Henry P, Joshi P, Powles ACP, Sherkey JA, van de Sande MI (2003). "Myalgic encephalomyelitis/chronic fatigue syndrome: Clinical working definition, diagnostic and treatment protocols". Journal of Chronic Fatigue Syndrome 11 (1): 7-36.

3) Jason LA, Porter N, Shelleby E, Bell DS, Lapp CW, Rowe K, & De Meirleir K. (2008). A case definition for children with Myalgic Encephalomyelitis/ chronic fatigue syndrome. Clinical Medicine: Pediatrics, 1, 53-57.

4) Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. 1994 Dec 15;121(12):953-9.

5) Twisk FN, Maes M. A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS. Neuro Endocrinol Lett. 2009;30(3):284-99.

6) Kindlon T, Goudsmit EM. Graded exercise for chronic fatigue syndrome: too soon to dismiss reports of adverse reactions. J Rehabil Med. 2010 Feb;42(2):184; author reply 184-6.

7) Jason LA, Corradi K, Torres-Harding S, Taylor RR, & King C. Chronic fatigue syndrome: The need for subtypes. Neuropsychology Review 2005, 15, 29-58.

8) Kindlon T. Stratification using biological factors should be performed in more CFS studies. Psychol Med. 2010 Feb;40(2):352. Epub 2009 Oct 12.




Citaten uit het uitgebreide studieverslag



In this review, we examine the lessons learned from dangerous exercise,

particularly in the sense that exercise can elicit

an immunological danger type of stress and inflammatory response that,

under certain circumstances, becomes dysregulated and detrimental to health.




Lymphocytes, monocytes, and natural killer (NK) cells

increase rapidly with the onset of exercise

but begin to decrease immediately on its cessation.

Circulating neutrophils increase more slowly and

may remain elevated for up to several hours,

long after the initiating bout of exercise ends.




Indeed , in studies that have attempted

to compare the inflammatory response to exercise with psychosocial stress,

exercise was found to alter immune mediators far more profoundly.




There is even evidence that

exercise may be accompanied by

translocation of gut bacteria into the central circulation,

causing a classic antigen-mediated systemic immune response.




In particular, lymphocytes obtained from peripheral blood in asthmatics demonstrate

a predominance of T-helper lymphocyte type 2 (TH2, IL 4 producing) immune responses

relative to TH1 (IFN-γ producing).




This idea is corroborated by recent work from Frampton and coworkers showing that

exposure to ultrafine particles in air pollution (100 nm)

in combination with exercise

can influence activation of

circulating lymphocytes and expression of key adhesion molecules

like ICAM-1 on other leukocytes.




Dangerous exercise:

lessons learned from dysregulated inflammatory responses to physical activity.

J Appl Physiol. 2007 Aug;103(2):700-9. Epub 2007 May 10. doi:10.1152/japplphysiol.00225.2007.

Cooper DM, Radom-Aizik S, Schwindt C, Zaldivar F Jr.






an immunological "danger" type of stress and

inflammatory response


on occasion,

becomes dysregulated and

detrimental to health.


Examples include


exercise-induced asthma,

overuse syndromes, and

exacerbation of intercurrent illnesses.


In dangerous exercise,

the normal balance

between pro- and anti-inflammatory responses

is upset.


A possible pathophysiological mechanism

is characterized by

the concept of

exercise modulation of

previously activated leukocytes.


In this model,

circulating leukocytes

are rendered more responsive than normal

to the immune stimulus of



For example,

in the case of exercise anaphylaxis,

food-sensitized immune cells

may be relatively innocuous

until they are redistributed

during exercise

from gut-associated circulatory depots,

like the spleen,

into the central circulation.


In the case of asthma,

the prior activation of


may be the result of

genetic or

environmental factors.


In the case of overuse syndromes,

the normally short-lived neutrophil


because of acidosis and hypoxia,

inhibit apoptosis and

play a role in

prolongation of inflammation

rather than healing.


Dangerous exercise

demonstrates that

the stress/inflammatory response

caused by physical activity is robust and

sufficiently powerful,


to alter subsequent responses.


These longer term effects

may occur through as yet unexplored mechanisms

of immune "tolerance" and/or

by a training-associated reduction

in the innate immune response

to brief exercise.


A better understanding of

sometimes failed homeostatic physiological systems

can lead to

new insights

with significant implication for clinical translation.



PMID: 17495117 [PubMed - indexed for MEDLINE]



inflammation; innate immunity; leukocyte; asthma