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Effect of mitogen concentration on glucocorticoid suppression of normal and cystic fibrosis lymphocyte activation
Authors:Clark W Distelhorst  Barbara M Benutto  James M Corry
Institution:Department of Pediatrics, Washington University School of Medicine, St. Louis Children''s Hospital, St. Louis, Missouri 63110 U.S.A.
Abstract:It has previously been demonstrated that glucocorticoid suppression of mitogen-induced lymphocyte activation is a function of mitogen dose. Glucocorticoids suppress lymphocyte activation more at low doses, which induce suboptimal lymphocyte activation, than at higher doses which are optimal for lymphocyte activation. This observation suggests that glucocorticoid suppression of lymphocyte activation might be greater than normal in disease states which are associated with depressed mitogen-induced lymphocyte activation. To test this hypothesis, lymphocytes from normal individuals and patients with cystic fibrosis were activated by a full range of concentrations of concanavalin A (Con A) in the presence or absence of dexamethasone. Con A activation of cystic fibrosis lymphocytes was markedly depressed compared to the activation of normal lymphocytes at all doses of Con A, but the suppressive effect of dexamethasone on the activation of normal and cystic fibrosis lymphocytes was the same. We conclude that glucocorticoid suppression of lymphocyte activation is more a function of mitogen dose than of the level of lymphocyte activation and is not necessarily greater than normal in disease states which are associated with depressed mitogen-induced lymphocyte activation.
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