Journal of IiME Volume 6 Issue 1 (June 2012) of this response bears a relationship to the intensity of effort but many environmental factors also modulate cytokine release. The main source of exercised-induced IL-6 production appears to be the exercising muscle. Cytokine concentrations are increased in (ME)CFS. Exercise-induced modulations in cytokine secretion may contribute to allergies (and) bronchospasm” (Shepherd RJ. Crit Rev Immunol 2002:22(3):165-182). 2002 In 2002 an important book was published by CRC Press: “Chronic Fatigue Syndrome – A Biological Approach” edited by Patrick Englebienne and Kenny De Meirleir. It provides a technical treatise on the scientifically documented basis of (ME)CFS and includes advances not only in the immunology, but also in the virology, bacteriology, protein chemistry and biochemistry, physiology and metabolism, clinical biology, pharmacology and epidemiology of (ME)CFS. 2003 On 31st January – 2nd February 2003, the Sixth Biennial AACFS International Research and Clinical Conference was held at Chantilly, Virginia. The number of oral and poster presentations (44 and 47 respectively) was down from the 2001 conference (72 and 41 respectively) and from the 1999 conference (57 and 46 respectively), but the conference was attended by over 190 physicians and health professionals from more than 14 countries, including Professors Anthony Komaroff, Leonard Jason, Robert Suhadolnik, Benjamin Natelson, Charles Lapp and Dr Daniel Peterson. Dr Kevin Maher (University of Miami Medical School) described his work to determine the molecular mechanisms underlying the decreased NK cell cytotoxicity found in (ME)CFS patients, including activated T cells, elevated cytokines and immunoglobulins and reduced NK cell activity. His studies demonstrated significantly elevated expression of the activation molecule CD26 on Thelper cells and significantly reduced NK cell cytotoxicity relative to controls. His studies concluded that perforin and granzymes A and B (used by T cells for killing infected cells) were significantly reduced in the T cells of (ME)CFS Invest in ME (Charity Nr. 1114035) patients, and that activation of T cells is correlated with increased IL-4 and with decreased IL-6 that are typically seen in (ME)CFS patients. In addition, the data suggest that the cytotoxic defect may not be NK specific but may encompass the cytotoxic T cell subset as well (with grateful acknowledgement to Drs Charles Lapp, Rosamund Vallings and Neil Abbot). Dr Patrick Gaffney (Department of Medicine, University of Minnesota) demonstrated that white blood cells from patients with (ME)CFS exhibit distinct gene expression profiles, with differential regulation of 54 genes between patients with (ME)CFS and normal healthy controls. 2003 In Spring 2003 the Canadian Clinical Case Definition was published (“Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnosis and Treatment Protocols”. JCFS 2003:11(1):7-115). It was developed by an international Expert Consensus Panel of physicians who are world leaders in ME/CFS and who between them had diagnosed and/or treated more than 20,000 ME/CFS patients. It presents a systematic clinical working case definition that encourages a diagnosis based on characteristic patterns of symptom clusters that reflect specific areas of pathogenesis; in particular, it differs from previous definitions in that it includes the hallmark symptom of (ME)CFS (post-exertional fatigability and malaise) and requires the presence of pain, sleep disturbance and cognitive dysfunction, and at least one of the given symptoms from two of the categories of neurological/autonomic, neuro-endocrine and immune manifestations. The expert panel member specialising in immunology was Professor Nancy Klimas. It was widely acclaimed internationally by clinicians, scientists and patients alike, but in the UK the Wessely School actively opposed its use within the NHS and Departments of State, with the result that NICE recommended against its use in its 2007 Clinical Guidelines on “CFS”. (Markedly different from the situation in the UK, a commissioned Report to the New Zealand Ministry of Health, November 2003, found that: “Of all the www.investinme.org Page 64 of 108
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