Involvement of Lymphocytes in Non-immune Inflammation: Dual Effect of Glucocorticoids

Leucopenia induced by the administration of methotrexate reduced the volume of inflammatory exudate and the number of cells entering the pleural cavity during a 4-h carrageenin pleurisy when compared with that of non-leucopenic controls. The depressed response was partially but markedly restored when leucopenic animals were intravenously injected, immediately before the initiation of pleurisy, with spleen lymphocytes (or their products) obtained from normal, adrenal-demedullated or mock-operated rats. In contrast spleen lymphocytes (or their products) obtained from adrenalectomized rats or from rats receiving metyrapone, an inhibitor of adrenal glucocorticoid biosynthesis, were completely inactive. It is concluded that in physiologic concentrations glucocorticoids are essential for the production of lymphocyte-derived factors involved in the development of acute, non-immune inflammation. In pharmacologic concentrations, however, glucocorticoids suppress the release of such pro-inflammatory factors.