Journal of IiME Volume 2 Issue 1 www.investinme.org Essential investigations for people with ME/CFS? (Continued) U “Inflammation is not a stable condition. In a given individual it can fluctuate rapidly according to a number of environmental factors (e.g. stressors) and internal variables (e.g. diurnal variation of cortisol)”. “Basic aspects of diagnosis of behavioural disorders remain controversial and lack solid scientific foundations”. “In order to provide consistency, all studies examining the potential impact of inflammatory pathways should include a standard set of inflammatory biomarkers (which should include) the acute phase proteins, CRP, sialic acid and hatoglobin; the inflammatory mediators, prostaglandins E2 and C3A and the innate immune cytokine IL-6 as measured by the high sensitivity (hs)enzyme-linked immunosorbent assay (ELISA) in plasma. These biomarkers, especially hs-CRP and IL-6, have been found to reproducibly identify the presence of an activated immune response in a number of disorders. Most of these assessments can be run in certified commercial or hospital laboratories”. “There have been significant advances in imaging techniques during the past ten years (and) a variety of imaging techniques have enabled inflammation in the brain to be viewed in real time. However, except in conditions of severe systemic inflammation, signalling of systemic inflammation to the healthy brain does not involve structural damage”. “It is important to highlight the distinction between signalling by molecules typically associated with inflammation and an inflammatory response per se. During systemic inflammation there is induction of IL-1β and other proinflammatory cytokines, but there is no inflammatory response in the brain. It is of interest that microinjection of IL-1β into the brain at concentrations that would typically give rise to inflammation in peripheral tissues does not lead to typical inflammation within the brain parenchyma. This indicates that the biological significance of IL-1β in the brain parenchyma is different from that in other tissues”. “Although we have the necessary tools to image inflammation in the brain, it seems we do not have sufficiently sensitive tools to image signalling in the brain consequent to a systemic inflammatory response”. “Proinflammatory cytokines induce the production of Invest in ME (Charity Nr. 1114035) several downstream inflammatory mediators, such as prostaglandins and nitric oxide. Proinflammatory cytokines and other inflammatory mediators are produced by accessory immune cells, such as macrophages and monocytes in the periphery, and microglia within the central nervous system. Targeting cell trafficking into the central nervous system is unlikely to be a very useful approach since symptoms of sickness are dependent on the activation of brain cytokine signalling independently of any blood cell recruitment”. “Peripheral infections can sensitise or exaggerate existing brain inflammatory processes (and) elevated cytokine levels in blood have the potential to reverberate and activate central nervous inflammatory systems”. The Conclusions of the Review note the intense discussion at the meeting that resulted in a series of recommendations for improving understanding of the relationship between inflammation and subjective health complaints. These recommendations note that because inflammation-associated sickness symptoms are a major impediment to human health, research on the mechanisms and treatment of such symptom burden in physically ill patients should be strongly encouraged; that clinical tools for assessing inflammation-associated symptoms should be standardised; that there should be a minimum set of inflammatory biomarkers; that brain neuroimaging techniques should be used for revealing the brain structures that are influenced by peripheral inflammatory processes and whose ability to process information is impaired by excessive amounts of interoceptive stimuli (caused, it seems, not – as asserted by Wessely School psychiatrists -- by aberrant focusing on normal bodily sensations or by “remembered illness” but by inflammatory processes), and that presence of inflammation-associated symptoms ill patients provides a background against the high in physically which it is possible to test alleviating effects of therapies targeting immune-to-brain communication pathways. The Review notes that despite major advances in the understanding of the immune-to-brain communication pathways that underlie the pathophysiology of symptoms in inflammatory conditions, little has been done to translate this knowledge to the clinics. As NICE is now in the process of contacting selected people asking for their input on the advisability of it producing guidance on the use of Ampligen in “CFS/ME”, might NICE also be persuaded to seek the input of experienced vascular biologists on the advisability of it recommending specific testing for inflammation in ME/CFS? Page 34/34
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