We do know that rapamycin can cause interstitial lung disease. While we see benefits in some suppression of immune cytokines such as IL-6 and IL-11, a blanket suppression of cytokines may be damaging. Apparently suppressing IL-10 can cause lung damage.
IL-10 sensing by lung interstitial macrophages prevents bacterial dysbiosis-driven pulmonary inflammation and maintains immune homeostasis
https://www.cell.com/immunity/abstract/S1074-7613(25)00167-0
These cytokines are here for a reason. IL-10 is anti-inflammatory (even though it can cause senescence).
suppressing by how much?
The intro reads…
Loss of IL-10 signaling and animals lacking IL-10 signaling
Which is not exactly the same as “suppressing”
In November 2017, sirolimus was discontinued and she was switched to everolimus at 0.75 mg twice daily. The level was maintained at 4–8 ng/ml. Within one week the patient experienced improvement in her symptoms and she was back to her baseline level of activity after two months.
I never looked at everolimus until just now and I wonder why it’s not more popular with the longevity set? Since it has limited if no effect on mTORC2 it seems like it would be on the top of the list for mTOC1 inhibition.
One way to lose IL-10 signaling is to lower or suppress IL-10 levels. Wrt. everolimus, it’s a very complicated situation. I have been doing a deep dive into everolimus and can report that there are a ton of contradictory studies and claims around it - some claim that it impacts mTORC2 less than sirolimus, but others don’t. Some claim everolimus has a shorter half-life in humans, others claim that it’s sirolimus that’s shorter compared to everolimus. I personally am interested in it, because of possible brain benefits with BBB crossing (compared to sirolimus). I have an idea which is very “out there” and therefore requires a LOT of research - my idea is to slighly lower my sirolimus intake (f.ex. from 6mg/1-week to 5mg) and add 2mg everolimus mid-week. That way I’m hoping to capture the benefit of both without harmful or suboptimal interactions. YMMV. WIP - Work In Progress. Of course, should I decide to go forward, then it becomes a matter of sourcing everolimus, which with the Indian shipping situation is fraught at the moment.