What is the role of corticosteroids in immunosuppression after solid organ transplantation?

Updated: Jan 04, 2016
  • Author: Bethany Pellegrino, MD; Chief Editor: Mary C Mancini, MD, PhD, MMM  more...
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Answer

Answer

Corticosteroids are used for induction and maintenance immunosuppression, as well as for acute rejection. These agents prevent production of cytokines and vasoactive substances, including interleukin (IL)–1, IL-2, IL-6, tumor necrosis factor-α, chemokines, prostaglandins, major histocompatibility class II, and proteases. Corticosteroids act as agonists of glucocorticoid receptors but, at higher doses, have receptor-independent effects.

Glucocorticoid receptors are in cytoplasm in an inactive complex with heat shock proteins. The binding of corticosteroids to the glucocorticoid receptors dissociates heat shock protein from the glucocorticoid receptor. Formed active corticosteroid–glucocorticoid receptor complex migrates to the nucleus and dimerizes on palindromic DNA sequences in many genes. The binding of glucocorticoid receptors in the promoter region of the target genes can lead to either induction or suppression of gene transcripts.

The most common corticosteroids used in transplantation are oral prednisolone and intravenous methylprednisolone. These agents are metabolized by the liver and excreted by the kidneys as inactive metabolites. Drug interactions with P450 inhibitors and inducers are common.

Adverse effects of corticosteroids include cushingoid features, osteoporosis, avascular necrosis, cataracts, glucose intolerance, infections, hyperlipidemia, hypertension, peptic ulcer disease, pancreatitis, bowel perforation, weight gain, psychiatric disturbances, and growth restriction. Orofacial clefts and fetal adrenal suppression with corticosteroids have been reported in pregnancy.


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