Pharmacodynamic model for joint exogenous and endogenous corticosteroid suppression of lymphocyte trafficking.
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.
D000305:Adrenal Cortex Hormones / Q000494:pharmacology* / Q000502:physiology*; D000328:Adult; D001249:Asthma / Q000097:blood; D016516:CD4-CD8 Ratio; D002940:Circadian Rhythm / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D018655:Lymphocyte Count / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D008954:Models, Biological; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000502:physiology
D000305:Adrenal Cortex Hormones; D005938:Glucocorticoids; D006854:Hydrocortisone; D008775:Methylprednisolone