Exposure to systemic prednisolone for 4 hours reduces ex vivo synthesis ofGM-CSF by bronchoalveolar lavage cells and blood mononuclear cells of mildallergic asthmatics

Background In acute severe asthma, the earliest clinical effects of glucoco rticosteroids occur from 4 to 5 h after systemic administration, but the me chanisms are unclear. In persistent asthma, corticosteroids are thought to suppress airway inflammation by modulating the expression of adhesion molec ules, enzymes, and leucotactic cytokines, including granulocyte-macrophage colony stimulating factor (GM-CSF). GM-CSF is also overexpressed in the air ways of symptomatic asthmatics. Objectives To examine the early effects of systemic corticosteroids on cyto kine expression, we investigated whether ex vivo synthesis of GM-CSF is sup pressed in the bronchoalveolar lavage (BAL) cells and peripheral blood mono nuclear cells (PBMCs) of normal and mild allergic asthmatic subjects obtain ed 4 h after a single intravenous dose of prednisolone. Methods In a randomized, double-blind, placebo-controlled study, BAL cells and PBMCs were obtained from mild atopic asthmatic patients (n = 9) and nor mal subjects (n = 9) 4 h after an intravenous bolus dose of 80 mg prednisol one, and cultured for 0-18 h in the presence or absence of lipopolysacchari de (LPS; 10 mu g/mL). Enzyme immunoassay was used to assess GM-CSF levels i n BAL cell and PBMC culture supernatants, and in BAL fluid. Results After placebo, GM-CSF synthesis tended to be higher in BAL cells fr om asthmatics than in normals. LPS stimulation significantly increased medi an (interquartile range) GM-CSF synthesis by BAL cells ex vivo from 16.4 (2 3 to 74) to 35.8 (3-148) pg/10(6) cells in normals (P < 0.05), and from 59 (9 to 204) to 134 (24-288) pg/10(6) cells in asthmatics (P < 0.01). After i ntravenous prednisolone, the rise in GM-CSF production induced in BAL cells by LPS was completely abolished in both subject groups. In PBMCs of placeb o-treated asthmatics (but not normals), LPS stimulated median GM-CSF synthe sis from 164 (110 to 300) to 314 (235-485) pg/10(6) cells (P = 0.02), and t his was blocked by intravenous prednisolone. Conclusion LPS-stimulated GM-CSF synthesis ex vivo is abolished in BAL cell s of mild asthmatic and normal subjects, and in PBMCs of asthmatics, obtain ed 4 h after a single intravenous dose of prednisolone. Suppression of GM-C SF synthesis in airway and blood leucocytes may contribute to the early cli nical efficacy of systemic glucocorticoids in acute allergic asthma.