Mechanisms of corticosteroid action on lymphocyte subpopulations. I. Redistribution of circulating T and b lymphocytes to the bone marrow

Abstract

The effect of corticosteroid administration on the redistribution of sirculating lymphocytes was studied in the guinea-pig, since this species closely resembles man in its relative resistance to the lymphopenic effect of corticosteroids. A single intravenous injection of hydrocortisone (either 10 mg or 100 mg/kg) caused a profound but transient lymphocytopenia which was maximal at 4 hours following injection, with a returnto normal counts by 24 hours. There was a proportionately greater decrease in circulating T lymphocytes compared to B lymphocytes, although both populations were diminished. Chronic cortisone acetate treatment (100 mg/kg subcutaneously for 7 days) caused a similiar pattern of lymphocytopenia except that it was sustained during the period of chronically elevated plasma cortisol levels. The lymphocytes remaining inthe circulation during the period of lymphocytopenia responded normally in vitro to the mitogens phytohemagglutinin, concanavalin A, and pokeweek mitogen. There was very littleeffect of corticosteroid administration on the numbers, proportions, or mitogenic response of splenic lymphocytes. There was a dramatic increase in the bone marrow of proportions and absolute numbers of lymphocytes bearing surface T-and B-cell markers, as well as a marked increase in response of bone marrow lymphocytes to mitogenic stimulation during the period of maximal circulating lymphocytopenia caused by the administration of corticosteroids, especially chronic cortisone acetate. There was a preferential homing of reinfused -51Cr-labelled syngeneic peripheral blood lymphocytes to the bone marrow of corticosteroid-treated recipients. These studies demonstrate aredistribution of circulating lymphocytes to the bone marrow during corticosteroid treatment, resulting in an increase in immunocompetence of this compartment, while the peripheral blood lymphocyte compartment is quantitatively immunosuppressed due to a lymphocytopenia.