Copyright © 2008 Elsevier Ireland Ltd All rights reserved.
Opinion paper

Possible role for early-life immune insult including developmental immunotoxicity in chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME)

Rodney R. Dietertaa, and Janice M. Dietertbb
a Department of Microbiology and Immunology, C5-135 VMC, College of Veterinary Medicine, North Tower Road, Cornell University, Ithaca, NY 14853, USA
b Performance Plus Consulting, Lansing, NY 14882, United States
Received 25 November 2007; revised 6 January 2008; accepted 30 January 2008. Available online 8 February 2008.

Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME) in some countries, is a debilitating disease with a constellation of multi-system dysfunctions primarily involving the neurological, endocrine and immune systems. While substantial information is available concerning the complex dysfunction-associated symptoms of CFS, environmental origins of the disease have yet to be determined. Part of the dilemma in identifying the cause(s) has been the focus on biomarkers (hormones, neurotransmitters, cytokines, infectious agents) that are contemporary with later-life CFS episodes. Yet, recent investigations on the origins of environmental diseases of the neurological, endocrine, reproductive, respiratory and immune systems suggest that early life toxicologic and other insults are pivotal in producing later-life onset of symptoms. As with autism and childhood asthma, CFS can also occur in children where the causes are certainly early-life events. Immune dysfunction is recognized as part of the CFS phenotype but has received comparatively less attention than aberrant neurological or endocrine function. However, recent research results suggest that early life immune insults (ELII) including developmental immunotoxicity (DIT), which is induced by xenobiotics, may offer an important clue to the origin(s) of CFS. The developing immune system is a sensitive and novel target for environmental insult (xenobiotic, infectious agents, stress) with major ramifications for postnatal health risks. Additionally, many prenatal and early postnatal neurological lesions associated with postnatal neurobehavioral diseases are now recognized as linked to prenatal immune insult and inflammatory dysregulation. This review considers the potential role of ELII including DIT as an early-life component of later-life CFS.

Article Outline
  1. Introduction
  2. Age-relationships and implications for early-life CFS risk factors
  3. Early life link to CFS and other chronic diseases with immune-inflammatory dysfunction
  4. Environmentally induced origin of CFS dysfunction: immune, neurological and/or endocrine?
  5. The immune insult profile linked with CFS
    1. Overview
    2. Myelomonocytic cells and specific inflammatory mediator production
  6. CFS and baseline immune activation
  7. The inflammation–anti-inflammation dysfunctional cycle of cytokines
  8. Immune cytokine-induced sickness behavior and CFS symptoms
  9. Potential T helper bias
  10. Innate immunity-NK cells
  11. Virus infection and reactivation: CFS inducer, episode trigger, or reflection of immune status?
  12. Multi-factorial inducers of CFS—a possible model
  13. Conclusions
  14. Acknowledgements

Fig. 1.
Proposed model for risk factors of chronic fatigue syndrome (CFS) incorporating early life immune insults (ELII) including developmental immunotoxicity (DIT). Potential multi-factorial risk factors for CFS are shown above the developmental timeline. In utero or postnatal exposure to environmental chemical, drugs, infectious agents or other stressors induces adverse immune alterations. A major postnatal stress such as childhood trauma would fix the earlier life physiological disruption in the form of CFS. Additional childhood or adult triggers such as exposure to infectious agents, toxicants, or other stressors are necessary to elicit disease onset. Genetic background including gender plays a role as shown below the developmental timeline. This would determine the susceptible subset of the population where exposure to the risk factors would manifest as this disease.

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