Dear Ivane Abiatari,

Of current immunosuppressive mTOR inhibitors (sirolimus and everolimus) are less nephrotoxic. Calcineurin inhibitors (cyclosporine and tacrolimus) have a higher nephrotoxicity. I do not know the type of experiment that you will perform, maybe you could use mycophenolate mofetil!

Regards

mTOR inhibitors are usually not nephrotoxic whereas CNIs (tacrolimus, cyclosporine) have a narrow therapeutic index and are potent vasoconstrictors and usually result in AKI. Antiproliferative agents such as mycophenolate mofetil (MMF) or mycophenolate sodium (MPS) do not cause kidney injury. The most common side effects are gastrointestinal and bone marrow suppression. Prednisone or prednisolone should not cause kidney injury either.

It highly depends on your reason for asking the question - transplantation, systemic diseases, experimental use etc All immunosuppressives are toxic by their very nature and how differing side-effects even in the same family - for instance ciclosporin and gum hypertrophy, tacrolimus and new onset diabetes after transplantation (>ciclosporin), severe infections with sirolimus as compared to others - and once again, risk profile once again changes depending if your pregnant. The benefits outweigh risks esp on initiation but depending on avoidance statergies due to individual circumstances each have their pros and cons.

one dosis of cyclophosphamide (200 mg/Kg) can induce immunosuppression during 7-10 days.

regards

Sirolimus may cause proteinuria and may deterioate renal function, which is less aparent in the case of low dose Tacrolimus in combination with mycophenolate mofetil.

Dear Dr Abiatari,

It would be appropriate to let us know what kind of animal transplant model and the intervention you are planning to examine, because the type of immunosuppressive agents you wish to use can be decided based upon these factors.

Best wishes

BMS

I've used a 28 day model of daily ciclosporin 30mg/Kg subcut previously to produce patchy renal fibrosis but the mice are relatively healthy. CD1 are the most susceptible strains whilst C57/Bl6s are fairly resistant in my hands

It is better To name the toxicity which like to avoid in your animal model, since the immunosuppreesive agents are so many and they very in toxicity. For example, some are toxic to the renal system where others toxic to CNS etc..

Traditionally, at least 5 classes of oimmunosuppressive agents are knownt such as glcucorticoids cytotoxic drugs; antibodies, drugs act on immunsystem and others such as interferons, opioid, etc. Generally, certain medicinal plants provide may have low toxicity in providing some help to immunsystem such as Stachys obtusicrena, Salivia mirzaayanii, Punica granatum, Alfaala, Aloe, Rosemry, SaintJhon'swort etc,..

The researcher has to try any or combination, of such agent as trial and error to obtaine best results .Good luck.

Ivane, I see that you have sufficient or even too many answers but this is a general approach to an answer that you make for yourself. Choose the immunologic suppressive agent and continue longer time and higher dose until you get a major toxic effect and decide if the amount of immune suppression you want is at a much lessor dose than you have achieved. This is the general process in preclinical drug testing before a drug is approved by FDA. The time and cost of this approach will be the best investment to success with your prospective research. I think you; have all or more advice than needed but let me know if want more detail.

Bobby Payne DVM, MS. PhD. DACVP, Preclinical Drug Development Scientist, Retired

You need to define what part of the immune system you are interested in suppressing and how and where you want that suppression to occur. While there are a number of agents that can suppress immune system function, some are more selective than others in their action on specific immune system function.

I agree with all answers. It is up to you Ivane, to narrow down your objective of study and choose one of the immunossuppression. Again, most toxicities are dose dependent. You have to look into AUC for toxicity in experimental aanimaals to decide what dose you want to use. The other option is to use mice/rats with genetically engineered species to have sspecific immunodeficiency per se e.g. SCID -ve mice, etc. It depends upon your experimental design and aim of the study. Hope this will help.