Fluticasone propionate-induced regulation of the balance within macrophage subpopulations.
In asthma, treatment with inhaled corticosteroids reduces chronic peribronchial inflammation and restores the balance within macrophage subpopulations. This study investigates whether corticosteroids can regulate monocyte differentiation in vitro and thereby influence the balance of functionally distinct macrophages. Graded doses of fluticasone propionate (FP) were added to cultures of normal peripheral blood monocytes in the presence or absence of IL-4. Cells were harvested after 7 days' culture. Double immunofluorescence studies were performed on cytospins of differentiated macrophages using the MoAbs RFD1 and RFD7 to distinguish inductive and suppressive macrophages by their respective phenotypes. Macrophage function was determined by quantifying allostimulation in a mixed leucocyte reaction and by measuring tumour necrosis factor-alpha (TNF-alpha) production. FP reduced the number of mature cells with a D1+ antigen-presenting phenotype and up-regulated the 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 beneficial effect by normalizing the macrophage subset imbalance that contributes to the chronic peribronchial inflammation present in this condition.
Tormey
V J
VJ
Department of Immunology, Royal Free & University College School of Medicine, London, UK. rfim0007@rfhsm.ac.uk
Bernard
S
S
Ivory
K
K
Burke
C M
CM
Poulter
L W
LW
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D000730:Androstadienes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D000068298:Fluticasone; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008264:Macrophages / Q000145:classification / Q000187:drug effects* / Q000276:immunology*; D010641:Phenotype; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000305:Adrenal Cortex Hormones; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000068298:Fluticasone