Cyclosporine: mechanisms of action and toxicity.

Abstract:

BACKGROUND:Newer immunosuppressive agents are permitting transplantation to be performed more frequently. OBJECTIVES:To review the mechanisms of action and toxicity of cyclosporine. DISCUSSION:Graft rejection is mainly cell-mediated, although a humoral (antibody) response may also be involved. Cyclosporine and related agents such as FK-506 and rapamycin selectively inhibit adaptive immune responses by blocking T cell-dependent biosynthesis of lymphokines, particularly interleukin 2 at the level of messenger ribonucleic acid (mRNA) transcription. Because cyclosporine is metabolized in the liver by P-450 enzymes, drugs that affect the P-450 system also affect the metabolism of cyclosporine. Hypertension is the most common side effect of cyclosporine. Cyclosporine-induced "nephrotoxicity" may be functional rather than anatomic, caused primarily by preferential constriction of the afferent renal arteriole. Bacterial and fungal infections are less common with regimens of cyclosporine plus prednisone than with azathioprine plus prednisone. Nevertheless, cyclosporine-treated patients are vulnerable to viral infections. CONCLUSIONS:Although cyclosporine and related compounds represent an improvement over earlier immunosuppressive agents, they produce serious side effects with which the practitioner should be familiar.

journal_name

Cleve Clin J Med

authors

Graham RM

doi

10.3949/ccjm.61.4.308

subject

Has Abstract

pub_date

1994-07-01 00:00:00

pages

308-13

issue

4

eissn

0891-1150

issn

1939-2869

journal_volume

61

pub_type

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