The role of rapamycin as an immunosuppressant is very complex and misunderstood. Much of that is due to the complexity of the immune system itself.
Rapamycin works in a paradoxical manner. On the one hand it supresses the proliferation of naïve T cells, allowing for an alleviation of the host/ graft transplant reaction. Because this is commonly described as immunosuppression, the fear is that it will increase the risk , and severity, of infections.
Renal transplant patients are very prone to a resurgence in cytomegalovirus infections, which can be quite serious. Interestingly, those patients on rapamycin fared much better against CMV than those treated with other agents.
Here’s the paradox. Rapamycin was found to actually increase a subset of T cells known as CD8+ memory cells. This is particularly true in the quality of their functioning. This was very protective against CMV.
Of further interest, rapamycin was found to increase the immune response to viral vaccines in both mice and monkeys. And not just viruses, but also in mice , there was an augmented response to the mycobacterium TB vaccine.
Furthermore, for the first time, Mannick et al showed a similar response in aging humans from just a low dose of everolimus. In this study it was proposed that rapamycin rejuvenated the T cell population by reducing the percentage of detrimental PD1 T cells which accumulate as we age. This lead to a beneficial response to the flu shot.
At present, there seems to be a general sense that rapamycin protects against viruses, but predisposes to bacterial infections. This appears to be mainly from statements made by Alan Green presumably based on clinical experience. There doesn’t seem to be any other evidence for this risk, especially in those using the drug intermittently.
We need to remember that bacterial infections like sinusitis, bronchitis, and cellulitis, are very common and would be highly prevalent in a control group. Also, it’s very likely that in a very elderly population, like those treated by AG, that polypharmacy is in play and would make it difficult to implicate rapamycin.
As an example of this, I recently saw a hospitalized patient with a severe pneumonia at the age of only 52. She took rapamycin 3 mg once weekly for anti aging purposes. It was therefore assumed that rapamycin was a contributing factor, if not the sole factor, in her infection, which was bacterial in origin. However, on further evaluation, she was also on clozapine which is a known risk factor for severe bacterial pneumonias.
So I would say that we need to define rapamycin as an immunomodulator which acts in a paradoxical manner on the immune system and shows no clear evidence of infection risk, either viral or bacterial, at this time. This is especially true in the intermittent usage group for anti aging purposes.
