Journal of IiME Volume 6 Issue 1 (June 2012) compared to controls: LT, IL-1, IL-1, IL-4, IL-5, IL-6, and IL-12. The following cytokines were decreased in (ME)CFS: IL-8, IL-13 and IL-15. Cytokine abnormalities are common in (ME)CFS. In this study, 10 of 16 cytokines examined showed good to fair promise as biomarkers. However, the cytokine changes observed are likely to be more indicative of immune activation and inflammation, rather than specific for (ME)CFS….Many of the symptoms are inflammatory in nature….A significant elevation in the relative amounts of 4 of 5 proinflammatory cytokines in peripheral blood plasma of patients with (ME)CFS was found when compared with the controls….In cases, lymphotoxin (LT) was elevated by 257% and IL-6 by 100% over the controls. (The antiinflammatory cytokine) IL-13 was significantly lower (15%) in (ME)CFS patients….IL-12 was significantly elevated (120%) and IL-15 decreased 15% in cases compared to controls. (The chemokine) IL-8 (CXCL8) was 42% lower in the (ME)CFS patients….In the (ME)CFS cases we found an unusual pattern of the cytokines that define the CD4 T cell….Allergy is common in (ME)CFS cases….The decreased NK cell cytotoxic and lymphoproliferative activities and increased allergic and autoimmune manifestations in (ME)CFS would be compatible with the hypothesis that the immune system of affected individuals is biased towards a T-helper (Th) 2 type, or humoral immunity-orientated cytokine pattern. The elevations in LT, IL-1, IL-1 and IL-6 indicate inflammation, likely to be accompanied by autoantibody production, inappropriate fatigue, myalgia and arthralgia, as well as changes in mood and sleep patterns….Cytokine abnormalities appear to be common in (ME)CFS. Several showed promise as potential biomarkers. The changes from the normal condition indicate immune activation and inflammation….The data from this study support a Th2 shift, pro-inflammatory cytokine upregulation and down-regulation of important mediators of cytotoxic cell function” (Mary Ann Fletcher, Nancy Klimas et al. Journal of Translational Medicine 2009: 12th November:7:96). 2010 Invest in ME (Charity Nr. 1114035) The fifth Invest in ME International Conference was held on 24th May 2010 in London. The immunological aspects of ME/CFS were discussed by Professor Nancy Klimas (Miami), who informed attendees that there is already a biomarker for ME/CFS – NK cell function. This should be considered to be a consistent finding in ME/CFS patients, and it is a good indicator of severity; it is also useful in defining sub-groups. As an NK cell abnormality is not unique to ME/CFS, it cannot be used as a diagnostic biomarker, but NK cell cytotoxicity does appear to be a marker of disease activity in subgroups. The main theme of her presentation was the need to find biomarkers involved with the immune dysfunction seen in ME/CFS patients. She summarised important markers of immune activation:  An elevated proportion of CD26 lymphocytes (a specific type of white blood cell) expressing the activation marker dipeptidase IV (DPPIV)  Polarisation of the Th-2 (helper type 2) immune response  Elevation of pro-inflammatory cytokines such as TNF, interleukin 1 (IL-1) and IL-6 (a cytokine of marked inflammation)  Important defects in immune system function (especially NK cytotoxicity), CD8 and macrophage abnormalities and antibody production. Professor Klimas also referred to new research showing that CD26 lymphocyte activation can lead to the production of neuropeptide Y (NPY), which acts on adrenaline responses in the sympathetic nervous system, i.e. on the autonomic control of heart, bladder and bowel function (with acknowledgement to Dr Charles Shepherd). 2010 “(ME)CFS is a multifactorial disorder that affects various physiological systems including immune and neurological systems….The objective of this present study was to determine deficiencies in lymphocyte function and erythrocyte rheology in (ME)CFS….Immune dysfunction may therefore be an important contributory factor to the mechanism of (ME)CFS, as indicated by decreases in neutrophil respiratory burst, NK cell activity and NK phenotypes. Thus, immune cell function www.investinme.org Page 87 of 108

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