Fluticasone propionate-induced regulation of the balance within macrophagesubpopulations

In asthma, treatment with inhaled corticosteroids reduces chronic peribronc hial inflammation and restores the balance within macrophage subpopulations . This study investigates whether corticosteroids can regulate monocyte dif ferentiation in vitro and thereby influence the balance of functionally dis tinct macrophages. Graded doses of fluticasone propionate (FP) were added t o cultures of normal peripheral blood monocytes in the presence or absence of IL-4. Cells were harvested after 7 days' culture. Double immunofluoresce nce studies were performed on cytospins of differentiated macrophages using the MoAbs RFD1 and RFD7 to distinguish inductive and suppressive macrophag es by their respective phenotypes. Macrophage function was determined by qu antifying allostimulation in a mixed leucocyte reaction and by measuring tu mour necrosis factor-alpha (TNF-alpha) production. FP reduced the number of mature cells with a D1(+) antigen-presenting phenotype and up-regulated th e development of cells with the D1/D7(+) and D7(+) phenotypes. Functionally , this was associated with reduced stimulation of T cell proliferation in a mixed leucocyte reaction (MLR). Fluticasone also reversed the increase in both D1(+) expression and TNF-alpha production induced by IL-4. The effect of FP persisted for 24 h after removal of FP from the culture medium. These results suggest that FP treatment of asthmatics may have a direct benefici al effect by normalizing the macrophage subset imbalance that contributes t o the chronic peribronchial inflammation present in this condition.