Journal of IiME Volume 6 Issue 1 (June 2012) improved and those who did not improve following exposure to non-pharmacologic interventions….Past research has shown that CFS is associated with a shift toward a Type 2 immune response, and in the present study, those with this pattern tended not to improve….In other wards, a dominance of the Type 2 over Type 1 immune response, as indicated by the patterns of lymphocytes subset distributions among those with CFS, did not improve over time….The current study further supports the contention that clinically distinct subsets of patients within the current definition of CFS….Such differences…highlight the need to define clinical subsets in CFS….Subgrouping is the key to understanding how CFS begins (and) how it is maintained” (Leonard A Jason, Mary Ann Fletcher et al. Tropical Medicine and Health 2008: 36:1:2332). 2008 “The main hypotheses include altered central nervous system functioning resulting from an abnormal immune response against a common antigen….This review discusses the immunological aspects of (ME)CFS and offers an immunological hypothesis for the disease process….Present data from various sources support the model that (ME)CFS has a propensity to over-produce proinflammatory cytokines, coupled with a misregulation of anti-inflammatory cytokines….These immunological findings show that patients with (ME)CFS may have an infection and that the immune system is chronically activated in response. Several of the differentially expressed genes are related to immunological functions and implicate immune dysfunction in the pathophysiology of the disease” (Lorenzo Lorusso et al. Autoimmunity Reviews 2008: doi:10.1016/j.autrev2008.08.003). 2008 “(ME)CFS is a neuro-immune disorder linked to chronic immune activation and dysregulation of the HPA axis….Upsets in immune demographics are reflected in cell-cell signalling and elevated levels of pro-inflammatory cytokines such as INF and TNF- in (ME)CFS. The HPA axis is central in modulating this inflammatory response through the synthesis of cortisol via a cascade involving Invest in ME (Charity Nr. 1114035) adrenocorticotrophic hormone (ACTH) and corticotropin-releasing hormone (CRH)….Accordingly HPA axis dynamics are tightly coupled with those of the immune system….(ME)CFS patients inhabit a stable hypocortisolic state highly conducive to the emergence of chronic inflammatory immune signalling….The reported changes in connectivity of immune functional nodes align well with observations of altered immune activity in (ME)CFS….We have successfully constructed association networks demonstrating the key role of immune function in (ME)CFS” (Jim Fuite, Suzanne D Vernon, Gordon Broderick. Genomics 2008:92:6:393-399). 2008 “(ME)CFS is characterised by immune dysfunctions including chronic immune activation, inflammation, and altered cytokine profiles. T helper 17 (Th17) cells belong to a recently identified subset of T helper cells, with crucial regulatory function in inflammatory and autoimmune processes. Th17 cells are implicated in allergic inflammation, intestinal diseases, central nervous system inflammation, disorders that may all contribute to the pathophysiology of (ME)CFS…To investigate the role of Th17 cells, and more specifically of the cytokine IL-17F, in the pathogenesis of (ME)CFS, we studied the association between (ME)CFS and the frequency of the IL17F His161Arg variant…We found a significantly lower prevalence of the His161Arg variant in the (ME)CFS population compared to the control population… The His161Arg variant antagonises the pro-inflammatory effects of…IL17F, and thereby exerts a protective effect against asthma. Similarly, we can make the hypothesis that the development and/or maintenance of (ME)CFS involves an increase in the production of IL-17F, and that the expression of the inactive variant confers protection against the disease (an expression that is significantly lower in patients with (ME)CFS)….(Our) results suggest a role of TH17 in the pathogenesis of (ME)CFS…The proinflammatory effects of Th-17-secreted cytokines are also consistent with other specific dysfunctions observed in (ME)CFS patients: IL-17 and IL-22 can disrupt the blood-brain barrier; Th17 lymphocytes transmigrate across the blood-brain barrier endothelial cells and promote inflammation of the www.investinme.org Page 82 of 108
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