Modification of the murine immune system by glucocorticosteroids: alterations of the tissue localization properties of circulating lymphocytes.

Glucocorticosteroids have proven capable of suppressing both developing and ongoing immune responses via mechanisms that are not fully understood. Most investigations into the mechanisms of glucocorticosteroid-mediated immunosuppression have examined the direct effects of these agents on the lymphocyte itself. In this paper, we have analyzed the effects of glucocorticosteroids on the lymphocyte receptive capacity of lymph nodes and bone marrow in mice. These effects appear to be mediated via reversible changes in the capacity of steroid-treated vascular endothelial cells to interact with normal lymphocytes, and are both dose and time dependent. The most striking effects on lymphocyte localization were observed in mice given microgram quantities of glucocorticosteroids over a 6-day period via a continual release pellet. The direct exposure of lymphocytes to these drugs in vitro was shown to have no effect on their subsequent localization potential in vivo. Further studies revealed that the ability of antigen-sensitized effector lymphocytes to localize into sites of antigen deposition was also markedly depressed in mice pretreated with glucocorticosteroids. Therefore, steroids also appear to have effects on tissue associated endothelial cells which prevent the localization of sensitized effector lymphocytes into sites of active inflammation. Our observations have potential clinical implications, both in understanding the anti-inflammatory effects of glucocorticosteroids more fully, as well as suggesting that low-dose continual-release steroid administration may result in enhanced immunosuppression.