I’m very interested in Rapamycin and would like to try it. However, I have asthma and I’m concerned about its pro-inflammatory effects, namely increases in IL-12 and decreases in IL-10 which suggests an immunostimulatory response. Can anyone respond to this?
I think you are referring to this statement in the Wikipedia entry on sirolimus - am I right?
Sirolimus has complex effects on the immune system—while IL-12 goes up and IL-10 decreases, which suggests an immunostimulatory response, TNFand IL-6 are decreased, which suggests an immunosuppressive response. The duration of the inhibition and the exact extent to which mTORC1 and mTORC2 are inhibited play a role, but are not yet well understood.
My understanding is that rapamycin is really immunomodulatory in action - depending upon dosing. In some clinical studies using rapalogs (virtually identical to sirolimus) they increase immune system functioning.
At the dosing level and frequency that most of us here are using (4mg to 10mg, once dosed per week) most of us find rapamycin is anti-inflammatory. Many of us have stories of aches and pains going away entirely after starting rapamycin. If side effects are a concern, you may want to review what people have been reporting: Side Effects of Rapamycin (part 2)
Do you have any pre-existing conditions you are concerned about, and potential interactions with other prescribed medications?
I encourage you to review this paper:
mTOR inhibition improves immune function in the elderly
Inhibition of mTOR signaling extends life span and delays the onset of aging-related diseases in all species studied to date. These findings suggest that the mTOR pathway regulates aging. However, it is unknown if mTOR inhibition has beneficial effects on aging in humans. To begin to address this question, Mannick et al. evaluated the effects of the mTOR inhibitor RAD001 on the decline in immune function that occurs during aging in humans. Their findings suggest that RAD001 improved immune function in elderly volunteers as assessed by response to influenza vaccination. It remains to be determined whether mTOR inhibition improves additional aging-related conditions in humans.
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Thanks for the reply. Yes, I borrowed that sentence from Wikipedia, and yes, my pre-existing condition is asthma. My first rapamycin dose was 4 mg. The following 36 hours I experienced an exacerbation of my symptoms. Then, for about 12 hours after that, I had the best breathing I’d had in a long time. Still, the experience left me feeling wary of continuing to use it and I haven’t. I’ve spent countless hours reading about it but there too, the biochemistry is so complex I’m unable to fully understand it. If I try it again, I would not do more than 2mg, maybe once-a-week or maybe every other day. It’s really the Wild West with rapamycin, everyone is flying blind, more-or-less. In any event, I appreciate the effort you’ve expended to put up this fine site.
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Many of us start low here - e.g. 1mg once per week, and then slowly increase as we get comfortable with it, and see our body’s reaction. You might also take that approach.
I know absolutely nothing about asthma, but perhaps other people with more knowledge here can chime in and add their thoughts.
Yes - in most cases we are flying pretty blind with rapamycin. Not much is known about its longer term effects in healthy humans, even if all the animal data is very positive.
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This would seem to suggest that rapamycin might be helpful in preventing asthma… given that rapamycin is a very good mTOR inhibitor.
Activation of the mTOR signaling pathway is required for asthma onset
The mTOR pathway has been implicated in immune functions; however, its role in asthma is not well understood. We found that patients experiencing an asthma attack, when compared with patients in asthma remission, showed significantly elevated serum mTOR pathway activation, increased Th17 cells and IL-4, and decreased Treg cells and IFN-γ. In patients experiencing asthma, mTOR activation was positively correlated with the loss of Th17/Treg and Th1/Th2 balance. The role of mTOR in asthma was further confirmed using an ovalbumin-induced asthmatic mouse model. The mTOR pathway was activated in asthmatic mice, demonstrated by elevated levels of p-PI3K, p-Akt, p-mTOR, and p-p70S6k, and this activation was significantly reduced by treatment with budenoside or mTOR pathway inhibitors.
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Thank you! I will read the article.
I heard Masterjohn say Asthma is caused by insufficient glutathione in the lungs. Glutathione can be helped by eating foods with glutathione, supplementing with glutathione, or supplementing with NAC & glycine.
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Thank you, yes, I do supplement with the products you mention, but the results are mixed at best.
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