MECHANISM OF ACTION AND PURPOSE OF THE COMMONLY USED IMMUNOSUPPRESSANTS AFTER RENAL TRANSPLANTATION

Edited by, JASPER VICTORIA

Immunosuppressant drugs aid the recipient after organ transplantation by decreasing the actions of the body's immune system to prevent the rejection of the newly transplanted kidney. 

THE FOLLOWING ARE THE COMMONLY USED IMMUNOSUPPRESSIVE AGENTS USED AFTER ARENAL TRANSPLANTATION,

Steroids

The steroids inhibit gene transcription and the functions of t-cells, macrophages and neutrophils by bindimg to steroid receptors. They are used as prophylaxis and for the reversal of  transplant rejection.

Ciclosporin

Ciclosporin inhibits the T-cell activation and interleukin-2 synthesis by inhibition of calcineurin through formation of Ciclosporin-Cyclophilin ( an intracellular protein) complex. These are used for long term maintenance therapy against the rejection of transplant.

Tacrolimus

Tacrolimus also forms a complex with an intracellular protein and hence works by inhibiting calcineurin. It is used as the rescue therapy in severe or refractory rejection of transplants  and also as a long term maintenance therapy against transplant rejection.

Sirolimus

It inhibits B cells and blocks T-cell cycling due to the inhibition of signalling of interleukin-2. It is usually used in combination with cyclosporin with or without the addition of steroids.

Mycophenolate

It inhibits T-cell and B-cell function by reduction of nucleic acid synthesis due to the inhibition of the enzyme inosine monophosphate dehydrogenase. It is also used in combination with tacrolimus or ciclosporin with or without the addition of steroids.

Azathioprine

It gets incorporated in the DNA as purine and inhibits the proliferation of lymphocytes and neutrophils.

Muromonab

It is a mouse monoclonal anti-CD-3 antibody. It inactivates or kills the T cells by binding to the CD-3 complex. It has a short half-life. It is used as a prophylaxis and for the reversal of severe transplant rejection.

Anti-thymocyte / anti-lymphocyte globulin

It is polyclonal and derived from horse or rabbit. These alter the T-cell and B-cell activity by acting as the antibodies to lymphocyte proteins. These are also used as prophylaxis and for reversal of severe transplant rejection.

Basiliximab / Daclizumab

These are monoclonal antibodies that bind to CD25 of the IL-2 complex and therefore prevent T cell proliferation. It is used in combination with ciclosporin and steroids as prophylaxis against acute transplant rejection.