Review Cytokine, Sickness Behavior, and Depression, 2009, Dantzer

Abstract:

Sufficient evidence is now available to accept the concept that the brain recognizes cytokines as molecular signals of sickness. Clarifying the way the brain processes information generated by the innate immune system is accompanied by a progressive elucidation of the cellular and molecular components of the intricate system that mediates cytokine-induced sickness behavior. We are still far, however, from understanding the whole. Among the hundreds of genes that proinflammatory cytokines can induce in their cellular targets, only a handful has been examined functionally. In addition, a dynamic view of the cellular interactions that occur at the brain sites of cytokine production and action is missing, together with a clarification of the mechanisms that favor the transition toward pathology.

Link:

https://pmc.ncbi.nlm.nih.gov/articles/PMC2740752/

 

I think this is the kind of lack of knowledge that ME's secret can hide in. ME's symptoms are similar to sickness behaviour, but SB isn't understood well enough to figure out what's happening. It would be helpful if they could measure PWME's cytokines and say "Yes, that's clearly sickness behaviour." or that it isn't.

 

So do I. I feel a possible hypothesis is that there is a negative feedback loop somewhere in the sickness response of pwME which leads the body to dysregulate itself in all sorts of ways possibly never managing to completely leave the “sickness response” state. Many of which might contribute as feedback loops and worsen each other, especially during the physical changes undergone during exertion.

 

I definitely think of ME in terms of feedback loops. Which ones though? There are so many in our incredibly complex bodies. I do think more effort should be made to follow up on reliable responses--positive and negative--to various factors. If a majority of PWME found some reliable benefit from supplemental BCAAs, for example, that would be something to follow up on. Better yet would be a reliable response to some chemical that isn't a common building block in the body. Finding how cuminaldehyde affected cells to block PEM would be easier than if it was a common amino acid that gets used in multiple ways in all cells.

 

If we knew, we probably wouldn’t be here.

In my opinion given the lack of findings, it’s probably related to a complex mix of factors which are very hard to understand from a human POV, and machine learning with large data samples is likelier to make sense of it.

 

Also do note that the author of this paper isn’t very ME informed.

ie.

https://www.cell.com/trends/neurosc...m/retrieve/pii/S0166223613001963?showall=true