Yes - Many researchers are now calling rapamycin an immunomodulator, based on the Mannick studies. But at higher doses, on a regular daily schedule, its well known for immune system suppression (historically, that is the primary use for the drug, in organ transplant patients).
My question that started this thread is really about the issue of the exact immune suppression profile of rapamycin at higher and regular dosing (anywhere from daily to every two weeks) of rapamycin (in healthy people).
The study hasn’t been done, but basically I’m talking about the need for an optimal dosing study for healthy humans on rapamycin. I’d like to understand better the exact trade-off on potential longevity benefits vs. potential reduction in immune suppression (and the risks associated with it).
There is little data on this really, other than a few cancer or related studies.
This is related to this thread: Ideas on Protocols for Testing Higher Rapamycin Doses
We do know that in a 10mg/day dosing study that there are records of fatalities (due to infections/Sepsis) and other life-threatening situations.
I’ve communicated with the researcher Dudley Lamming and he thinks we should be measuring TREGs (regulatory T cells, a measure of immune function), as people go up higher in doses: Regulatory T-cells: Purpose, Function & Development
And here is that case of a fatality with higher dose (10mg/day) Everolimus (a rapalog), see below:
Rapamycin is not a risk-free drug, especially as you increase doses above the regular 5 to 8mg dosing once per week level.
The most common Adverse Effects (AEs) of everolimus therapy were laboratory abnormalities (100% of patients) and infection complications (83 episodes in 15 patients). Infectious episodes of pharyngitis (67%), diarrhea (44%), stomatitis (39%), and bronchitis (39%) were the most common infections. They were mostly mild or moderate in severity (grade 1–2).
In two cases, life-threatening conditions related to mTOR inhibitor treatment were encountered. The first was classified as grade 4 pleuropneumonia and Streptococcus pneumoniae sepsis, whereas the second was classified as death related to AE (grade 5) Escherichia coli sepsis.
A 27-year-old woman with TSC was started on everolimus
treatment because of AML of the left kidney
(60 Å~ 48 Å~ 36mm in size). The other signs of TSC were
facial angiofibroma, hypomelanotic macules of the skin,
and shagreen patch. The diagnosis of TSC was made
12 years earlier when the patient underwent nephrectomy
because of a large tumor of the right kidney. The
patient received everolimus at a dose 10 mg/day and the
trough concentrations of the drug ranged from 4.08 to
5.08 ng/ml. After 3 months of everolimus therapy, a
reduction in AML was observed (40 Å~ 31 Å~ 20mm in
size). During treatment, hypercholesterolemia (309 mg/
dl) and transient leukopenia (3.2 Å~ 109/l) with neutropenia
(1.34 Å~ 109/l) was observed. She also reported
oligomenorrhea. After a gynecological consultation, a
functional ovarian cyst was identified and contraceptives
were prescribed. However, 2 weeks later, she was
admitted to the gynecological unit because of subabdominal
pain and an ovarian cyst (64 Å~ 53mm in seize)
on ultrasound examination. Torsion of the ovarian cyst
was suspected. On the day of admission, WBC was
9.2 Å~ 109/l, the absolute neutrophil count (ANC) was
6.6 Å~ 109/l, the hemoglobin level was 10.8 mg/dl, the
PLT count was − 275 Å~ 109/l, and the C-reactive protein
concentration was 8.0 mg/dl (normal < 5.0 mg/dl). The
patient was advised to continue intake of contraceptives
and everolimus. The next day, the general condition of
the patient aggravated. Her blood pressure was low (85-
/50mmHg). Her WBC and ANC decreased (WBC
−2.4 Å~ 109/l, ANC − 1.8 Å~ 109/l), whereas the hemoglobin
level (11.0 g/dl), the PLT count (185 Å~ 109/l), and coagulation
tests were normal. Computed tomography of the
abdomen and pelvis showed AML of the left kidney (size
as in the previous examination), an ovarian cyst measuring
65 Å~ 50 Å~ 40 mm, and fluid in the retroperitoneal
space with density of the blood. Further aggravation of
her general condition was observed. The patient was
transferred to the ICU and she died after 2 h with
symptoms of shock and multiorgan failure. Blood and
urine cultures collected when she was in the ICU were
positive for Escherichia coli.
Complications of mammalian target of rapamycin inhibitor anticancer treatment among patients with tuberous sclerosis complex are common and occasionally life-threatening
https://sci-hub.se/10.1097/CAD.0000000000000207
