The RFA grant is a quasi-legal document that lays out in some detail what types of research the NIH is interested in. In effect it is a promise from the Department of Health and Human Services (DHHS) that states what it will use the people’s money for. In order to understand exactly what the NIH is looking for, this overview will highlight and attempt to explicate different sections of the text. (Click here to read the full text of the RFA).
A Grant For CFS? - We might as well start at the title. Note that the grant is not for "Neuroimmune Mechanisms IN Chronic Fatigue Syndrome". It is for "Neuroimmune Mechanisms AND Chronic Fatigue Syndrome". Why not use the more inclusive ‘IN"? Does this suggest that the grant may fund proposals that explicate neuroimmune mechanisms but not necessarily in CFS? Or is this just a bit of paranoia?
"The goal of this request for applications (RFA).is to solicit applications .on the neuroimmune mechanisms involved in the pathogenesis and pathophysiology of Chronic Fatigue Syndrome (CFS) and spectrum disorders."
Yet notice that the RFA does not call for research into the neuroimmune mechanisms in CFS or spectrum disorders, it calls for research into the neuroimmune mechanisms involved in CFS and spectrum disorders. This presents an entirely different scenario: that of the RFA supporting studies examining neuroimmune mechanisms in general but not involving either CFS or spectrum disorder patients. As noted above, this has, in fact, been common practice at the NIH for a number of years now. The NIH has repeatedly used funds for CFS research for studies that examine processes that could conceivably underlie some of the problems of CFS but do not actually involve CFS patients. It’s basically a dodge to underwrite projects the NIH wants to see accomplished but doesn’t otherwise have the money to do so. Given the pitiful amount of funding available for CFS even in the best of times CFS advocates have been understandably riled when they see what little funding they have going to fund non-CFS studies. But would this happen in a grant that has been advertised specifically for CFS? Would they dare?
A Focus on ‘Stress’ - The emphasis throughout the RAF is on the effects of ‘stress’. This is made clear in the first paragraph when, after an elucidation of possible dysregulating elements in the central nervous system (CNS) and immune system, stress is the only item mentioned as a potential cause;
‘Stress affects the activities of many of these mediators. Physiologic functions altered by stress and the ability to respond to stress likely play a role in the clinical manifestations of CFS¼ Internal and external stressors lead to altered signaling in the central nervous and immune systems".
‘Stress’ is a pretty hot button term. The NIH clears up what it means by stress when it states that ‘stressors, including infection, enzyme, gene and cytokine abnormalities, hormonal fluctuations toxicant exposures that affect brain function,’ can trigger the ‘stress response’.
Nowhere is psychological stress mentioned. Indeed it is not stress the NIH is primarily interested in but the ‘stress response’. The stress response primarily involves two systems, the sympathetic nervous system (SNS) and the HPA axis, both of which work intimately with the immune system to modulate it (and vice versa).
These systems, which maintain the ‘homeostasis’of the body, are responsible for returning it to its normal operating state after an infection, exercise or other stressor has altered it. They play a major role even in such common activities as standing. They are at rest only when a healthy person is supine. By inhibiting the immune response the HPA axis prevents it from inflicting tissue damage or attacking the body. By inhibiting the pro-inflammatory response the SNS downgrades the activity of many immune mediators and cells that, left unchecked, can cause inflammation, high levels of oxidative stress, tissue injury, etc. The pro-inflammatory cytokines (IL-1B, IL-6, TNF-a) the immune system produces during infection are able to interact with the central nervous system (CNS) to produce what is called ‘sickness behavior’. Since many of the symptoms seen in CFS (fatigue, aching muscles, sore throat, altered sleep, etc.) can be evoked by these cytokines, a dysregulated neuroimmune interaction could be the source of them.
The NIH lays out six factors it is looking for in these applications; two of which are noteworthy.
Unfortunately the meaning of ‘influences’ is not made clear. Most studies in the past that have looked for risk factors in CFS have concentrated on psychological issues rather than biological ones.
Finally the NIH tells researchers it wants them to use the 2003 NIH sponsored conference, ‘Neuroimmune Mechanisms and CFS’, as a guide for the types of research it is interested in funding. Indeed much of the rest of the document is right out of the Conference proceedings.