kaffiend
Senior Member
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This is a not yet hot off the press (Jan 2012) review to appear in the journal Brain, Behavior and Immunity. It might be the best review on ME/CFS I've seen. I've pasted the abstract and conclusion/summary below. You'll note that the paper uses the term CFS and not ME. The distinction is important and your anger is shared but let's talk about something else. 
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Chronic fatigue syndrome, the immune system and viral infection
A.S. Bansala, A.S. Bradleya, K.N. Bishopb, S. Kiani-Alikhanc, B. Forda
a Dept. of Immunology, Epsom and St. Helier University Hospitals NHS Trust, Carshalton, Surrey, SM5 1AA and Chronic Illness Research Team, Stratford Campus, University of East London, London E15 4LZ, UK
b Division of Virology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
c Dept. of Immunology, Kings College Hospital, Denmark Hill London, UK
Received 8 April 2011; revised 14 June 2011; Accepted 28 June 2011. Available online 2 July 2011.
Abstract
The chronic fatigue syndrome (CFS), as defined by recent criteria, is a heterogeneous disorder with a common set of symptoms that often either follows a viral infection or a period of stress. Despite many years of intense investigation there is little consensus on the presence, nature and degree of immune dysfunction in this condition. However, slightly increased parameters of inflammation and pro-inflammatory cytokines such as interleukin (IL) 1, IL6 and tumour necrosis factor (TNF) ? are likely present. Additionally, impaired natural killer cell function appears evident. Alterations in T cell numbers have been described by some and not others. While the prevalence of positive serology for the common herpes viruses appears no different from healthy controls, there is some evidence of viral persistence and inadequate containment of viral replication. The ability of certain herpes viruses to impair the development of T cell memory may explain this viral persistence and the continuation of symptoms. New therapies based on this understanding are more likely to produce benefit than current methods.
Summary
There are major challenges in the analysis of immune function in a condition as heterogenous as CFS where the cause is unknown. Add to this the marked variability in symptom severity from day to day and from hour to hour and there is bound to be variation in the levels of proteins such as cytokines that have short half lives. Further complications are evident in the analysis of immune cells which can vary in number depending on time of day and even mild exertion. Moreover, it is now established that stress and sleep disturbance, which are common in CFS, can alter immune function. Couple this with the fragile nature of most cytokines demanding immediate blood separation and the marked variation in assay sensitivity and reproducibility and it is easy to understand why there is little consensus in the literature on the exact immune dysfunction in CFS. Nevertheless the CFS literature taken as a whole suggests mildly raised circulating pro-inflammatory cytokines and a skewing towards impaired cellular immunity. More work is needed to take into account the level of stress and sleep disturbance amongst the study population and to correlate the immune function with the patients perception of how severe their symptoms were at the time of immune analysis. Most importantly of all more longitudinal studies investigating immune function with changes in the severity of CFS symptoms are urgently needed. It is likely that viral infection(s) and immune dysfunction in CFS interact in a manner which perpetuates the conditions necessary for maintaining symptoms. Fig. 1 summarises the interplay between the important variables. It is likely that an initial viral infection or stress acting singly or in combination leads to a state of impaired cellular immunity, immune memory dysfunction and disturbed NK cell activity. This promotes reactivation of previously acquired EBV or related virus infection and wide dissemination of the original viral infection. EBV and other viral proteins stimulate the release of pro-inflammatory cytokines which contribute to fatigue, low grade fever, aching, disturbance of sleep and inactivity. The severity and prolonged nature of these symptoms encourages further stress leading to continued immune paresis and production of immune dysregulating viral proteins. The latter then perpetuate the immune dysfunction with continuation of symptoms. In view of the significant interaction between each of these areas, treatments targeting several areas simultaneously are more likely to be successful than those used selectively in one area.
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Chronic fatigue syndrome, the immune system and viral infection
A.S. Bansala, A.S. Bradleya, K.N. Bishopb, S. Kiani-Alikhanc, B. Forda
a Dept. of Immunology, Epsom and St. Helier University Hospitals NHS Trust, Carshalton, Surrey, SM5 1AA and Chronic Illness Research Team, Stratford Campus, University of East London, London E15 4LZ, UK
b Division of Virology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
c Dept. of Immunology, Kings College Hospital, Denmark Hill London, UK
Received 8 April 2011; revised 14 June 2011; Accepted 28 June 2011. Available online 2 July 2011.
Abstract
The chronic fatigue syndrome (CFS), as defined by recent criteria, is a heterogeneous disorder with a common set of symptoms that often either follows a viral infection or a period of stress. Despite many years of intense investigation there is little consensus on the presence, nature and degree of immune dysfunction in this condition. However, slightly increased parameters of inflammation and pro-inflammatory cytokines such as interleukin (IL) 1, IL6 and tumour necrosis factor (TNF) ? are likely present. Additionally, impaired natural killer cell function appears evident. Alterations in T cell numbers have been described by some and not others. While the prevalence of positive serology for the common herpes viruses appears no different from healthy controls, there is some evidence of viral persistence and inadequate containment of viral replication. The ability of certain herpes viruses to impair the development of T cell memory may explain this viral persistence and the continuation of symptoms. New therapies based on this understanding are more likely to produce benefit than current methods.
Summary
There are major challenges in the analysis of immune function in a condition as heterogenous as CFS where the cause is unknown. Add to this the marked variability in symptom severity from day to day and from hour to hour and there is bound to be variation in the levels of proteins such as cytokines that have short half lives. Further complications are evident in the analysis of immune cells which can vary in number depending on time of day and even mild exertion. Moreover, it is now established that stress and sleep disturbance, which are common in CFS, can alter immune function. Couple this with the fragile nature of most cytokines demanding immediate blood separation and the marked variation in assay sensitivity and reproducibility and it is easy to understand why there is little consensus in the literature on the exact immune dysfunction in CFS. Nevertheless the CFS literature taken as a whole suggests mildly raised circulating pro-inflammatory cytokines and a skewing towards impaired cellular immunity. More work is needed to take into account the level of stress and sleep disturbance amongst the study population and to correlate the immune function with the patients perception of how severe their symptoms were at the time of immune analysis. Most importantly of all more longitudinal studies investigating immune function with changes in the severity of CFS symptoms are urgently needed. It is likely that viral infection(s) and immune dysfunction in CFS interact in a manner which perpetuates the conditions necessary for maintaining symptoms. Fig. 1 summarises the interplay between the important variables. It is likely that an initial viral infection or stress acting singly or in combination leads to a state of impaired cellular immunity, immune memory dysfunction and disturbed NK cell activity. This promotes reactivation of previously acquired EBV or related virus infection and wide dissemination of the original viral infection. EBV and other viral proteins stimulate the release of pro-inflammatory cytokines which contribute to fatigue, low grade fever, aching, disturbance of sleep and inactivity. The severity and prolonged nature of these symptoms encourages further stress leading to continued immune paresis and production of immune dysregulating viral proteins. The latter then perpetuate the immune dysfunction with continuation of symptoms. In view of the significant interaction between each of these areas, treatments targeting several areas simultaneously are more likely to be successful than those used selectively in one area.
