Research on the immune system could shed light on the cause of chronic fatigue syndrome (CFS), including whether a pathogenic agent such as a virus or bacteria is involved. This was one conclusion reached by a panel of experts that convened in October for the third in a series of scientific symposia on CFS. The symposium was sponsored by The Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) Association of America, the U.S. Centers for Disease Control and Prevention (CDC) and the National Institutes of Health Office of Research on Women's Health (ORWH).

A number of studies have suggested involvement of the immune system in CFS. New findings include the discovery of autoantibodies in CFS patients, which has led to increased speculation that the illness may be an autoimmune disorder. Because many cases of CFS begin with a flu or mono-like illness, viruses, bacteria and toxins have also been studied as possible causes.  "The immune system may provide important clues to CFS, but it cannot be studied in isolation," said Kimberly Kenney, President & CEO of The CFIDS Association of America. "A new emphasis on multidisciplinary research to explore links between the immune, neuroendocrine and cardiovascular systems in CFS is crucial to developing a better understanding of this complex illness."

Following a day of presentations by experts from around the world, an independent panel composed of researchers and practitioners in many fields, including biostatistics, endocrinology, immunology, infectious disease, internal medicine, microbiology, psychiatry and rheumatology, developed a statement on the key issues surrounding the role of the immune system in CFS.

The panel agreed that:

• The immune system is involved in CFS.  There has been substantial published evidence that a large proportion of CFS patients have immunological abnormalities,  including increased natural killer cell activity, increased number or activated T cells, decreased lymphocyte stimulation and increased production of some pro-inflammatory cytokines, which act as chemical messengers between cells. The panel noted that the ability to understand the exact role these changes play in the development of CFS is constrained by major limitations in the studies conducted to date.
  
• Infections may also play a role. The panel concluded that direct and indirect evidence points to the involvement of active viral or bacterial infections in the development of some cases of CFS, although no single agent has been found in all patients. For example, studies have found persistent activity of Epstein-Barr virus and/or human herpesvirus 6 in up to 30% of CFS patients.
  
• CFS is a multisystem disorder. In addition to the immune system, the endocrine and autonomic nervous systems may be implicated in CFS. There is some evidence that CFS is associated with underactivity of the hypothalamic-pituitary-adrenal axis, which could explain findings of upregulation of the immune system and an increase in circulating cytokines. Reproductive hormones may also influence cytokine production and help account for clear differences in gender prevalence in CFS. The panel acknowledged that little is known about the influence of the immune or endocrine systems on autonomic function in individuals with the illness.
  
• Experimental models for CFS exist. The panel noted that some viral infections appear to trigger CFS-like symptoms and could be used as models for the study of immune dysfunction in CFS. Epstein-Barr virus (EBV) has been the best-studied experimental model to date. Other infectious agents that may serve as models include cytomegalovirus, Ross River virus, Q Fever and the newly described JHK virus. Abnormal levels of several cytokines have been associated with CFS, and the panel suggested changes in response to therapeutic administration of cytokines might provide another useful research model.
  
• More research is needed to define the immunological aspects of CFS. The panel outlined future research needs, including multiple site, longitudinal studies to: explore the possible association of infectious agents with the immunological profile seen in CFS; link immunological findings to symptoms and functional disability; and explore the use of anti-inflammatory cytokines, antivirals, antibiotics and immunomodulatory agents in the treatment of CFS. Panelists also suggested ways to overcome research barriers, such as establishing standardized methodology to differentiate between latent infections normally present in most individuals and those that are more frequently activated and associated with CFS symptoms.

The CFS assessment symposia series is designed to examine the role of the neurological, endocrine, circulatory and immune systems in CFS. The symposia gather experts to evaluate research findings, identify the most promising next steps for research, define research and funding priorities and create research collaborative teams.

The CFIDS Association of America, which developed the symposia series, is the nation's leading organization working to conquer this illness. Since 1987, the Association has invested nearly $12 million in education, public policy and research programs in its efforts to bring an end to the suffering caused by CFS.

The CDC protects people's health and safety by preventing and controlling diseases and injuries, provides credible information on critical health issues and promotes healthy living through strong partnerships with local, national and international organizations. The agency conducts a CFS research program under the auspices of the National Center for Infectious Diseases.

The ORWH promotes, stimulates and supports efforts to improve the health of women through biomedical and behavioral research. ORWH works in partnership with the NIH institutes and centers to ensure that women's health research is part of the scientific framework at NIH and throughout the scientific community.

CFS, also called chronic fatigue and immune dysfunction syndrome (CFIDS), is a debilitating and complex disorder characterized by profound fatigue, pain and cognitive problems that are not improved by bed rest and may be worsened by physical or mental activity.