Activation of the NLRP3 inflammasome in LPS-induced mouse fatigue and its relevance to CFS

Tunguska

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Well, mario linked this thread and this seems like where it should go (accidentally landed on this while searching for something unrelated, believe it or not):
http://www.impactjournals.com/oncot...age=article&op=view&path[]=17256&path[]=55230
Rapamycin regulates macrophage activation by inhibiting NLRP3 inflammasome-p38 MAPK-NFκB pathways in autophagy- and p62-dependent manners

Excessive and prolonged activation of macrophages underlies many inflammatory and autoimmune diseases. To regulate activation and maintain homeostasis, macrophages have multiple intrinsic mechanisms, one of which is modulation through autophagy. Here we demonstrate that autophagy induction by rapamycin suppressed the production of IL-1β and IL-18 in lipopolysaccharide- and adenosine triphosphate-activated macrophages at the post-transcriptional level by eliminating mitochondrial ROS (mtROS) and pro-IL1β in a p62/SQSTM1-dependent manner. In addition, rapamycin activated Nrf2 through up-regulation of p62/SQSTM1, which further contributed to the reduction of mtROS. Reduced IL-1β subsequently diminished the activation of p38 MAPK-NFκB pathways, leading to transcriptional down-regulation of IL-6, IL-8, MCP-1, and IκBα in rapamycin-treated macrophages. Therefore, our results suggest that rapamycin negatively regulates macrophage activation by restricting a feedback loop of NLRP3 inflammasome-p38 MAPK-NFκB pathways in autophagy- and p62/SQSTM1-dependent manners.
(it doesn't mesh into the other ideas very well)
 

pattismith

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Its a PDE4 (phosphodiesterase) inhibitor, which means it alters the cAMP/Ca++ balance. If I recall correctly, its been a while since I investigated this, it works by decreasing the degradation of cAMP.
interestingly, caffeine is also a PDE inhibitor.

in my own trials, I had only limited successes when using separately caffeine, T3 and corticosteroids, but found relief of my symptoms when using them altogether (probably because of an hypopituitarism, which results in lack of T3, epinephrine, and cortisol)