Dehydroepiandrosterone replacement in patients with Addison's disease has a bimodal effect on regulatory (CD4+CD25hi and CD4+FoxP3+) T cells
| Autor: | Sara A. J. Thompson, Amanda L. Cox, Alasdair Coles, Suzanne Curran, V. Krishna K. Chatterjee, Elli M. Gurnell |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male endocrine system medicine.medical_specialty Lymphocyte Immunology Dehydroepiandrosterone Administration Oral Lymphocyte proliferation medicine.disease_cause Lymphocyte Activation T-Lymphocytes Regulatory Autoimmunity Immunophenotyping Immune system Addison Disease Adjuvants Immunologic Internal medicine polycyclic compounds medicine Adrenal insufficiency Immunology and Allergy Humans Cells Cultured Cell Proliferation business.industry FOXP3 Forkhead Transcription Factors Receptors Interleukin-2 medicine.disease CD4 Lymphocyte Count medicine.anatomical_structure Endocrinology Addison's disease Leukocytes Mononuclear Cytokines Female business hormones hormone substitutes and hormone antagonists |
| Zdroj: | European journal of immunology. 35(12) |
| ISSN: | 0014-2980 |
| Popis: | Oral replacement of the near-total deficiency of dehydroepiandrosterone (DHEA) in patients with Addison's disease (adrenal insufficiency) enhances mood and well-being and reduces fatigue. We studied the immunological effects of 12 wk of oral DHEA treatment in ten patients with Addison's disease receiving their normal mineralo- and glucocorticoid hormone replacement. We found that baseline circulating regulatory T cells were reduced in Addison's disease patients compared to controls, a hitherto unrecognised defect in this disorder. Oral DHEA treatment had a bimodal effect on naturally occurring regulatory (CD4+CD25hiFoxP3+) T cells and lymphocyte FoxP3 expression. Oral DHEA replacement restored normal levels of regulatory T cells and led to increased FoxP3 expression. These effects were probably responsible for a suppression of constitutive cytokine expression following DHEA withdrawal. In contrast, oral DHEA treatment led to reduced FoxP3 expression induced by TCR engagement and so augmented the cytokine response, but without a bias towards the Th1 or Th2 phenotype. NK and NKT cell numbers fell during DHEA treatment, and homeostatic lymphocyte proliferation was increased. We conclude that DHEA replacement in Addison's disease has significant immunomodulatory properties and propose that it has a greater impact on the human immune system than would be expected from its classification as a dietary supplement. |
| Databáze: | OpenAIRE |
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