Abstract
The circadian pattern of the immune system correlates with that of circulating T-helper cells and inversely with cortisol concentrations. Corticosteroids, both endogenous and exogenous, cause lymphocyte dimunition in blood by retention of cells in the lymphatic circulation. A physiologic pharmacodynamic model was developed to describe changes in circulating lymphocytes as a function of both endogenous cortisol and methylprednisolone concentrations. The model was applied to T-helper and T-suppressor cell data collected from six asthmatic men during baseline, after single-dose, and after 6 days of 20 mg daily methylprednisolone. The model described all phases of the study well. Baseline circadian rhythm of lymphocytes was related to cortisol concentrations. Multiple-dosing of methylprednisolone caused apparent tolerance and decreased the sensitivity of lymphocytes to corticosteroids by 116% and markedly reduced endogenous cortisol concentrations. A 60% increase in circulating T-helper cells was observed which could be accounted for by dual changes in receptor sensitivity and endogenous cortisol.
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Supported by National Institutes of Health Grant 24211 from the National Institute of General Medical Sciences and by the Sandoz Pharmaceutical Research Fellowship in Immunology Therapeutics from the American College of Clinical Pharmacy for Dr. Milad.
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Milad, M.A., Ludwig, E.A., Anné, S. et al. Pharmacodynamic model for joint exogenous and endogenous corticosteroid suppression of lymphocyte trafficking. Journal of Pharmacokinetics and Biopharmaceutics 22, 469–480 (1994). https://doi.org/10.1007/BF02353790
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DOI: https://doi.org/10.1007/BF02353790