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

• Published in: Clinical and experimental allergy 1999-12, Vol.29 (12), p.1655-1662
• Main Authors: Cotter, T. P., Hood, P. P., Costello, J. F., Sampson, A. P.
• Format: Article
• Language: English
• Subjects: Adult; asthma; Asthma - drug therapy; Asthma - metabolism; Biological and medical sciences; bronchoalveolar lavage; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; Bronchoscopy; Double-Blind Method; glucocorticoids; Glucocorticoids - therapeutic use; granulocyte-macrophage colony stimulating factor; Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis; Humans; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; lymphocytes; Lymphocytes - metabolism; macrophages; Macrophages - metabolism; Medical sciences; monocytes; Monocytes - metabolism; Pharmacology. Drug treatments; prednisolone; Prednisolone - therapeutic use; Respiratory system
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1046/j.1365-2222.1999.00674.x

Background In acute severe asthma, the earliest clinical effects of glucocorticosteroids occur from 4 to 5 h after systemic administration, but the mechanisms are unclear. In persistent asthma, corticosteroids are thought to suppress airway inflammation by modulating the expression of adhesion molecules, enzymes, and leucotactic cytokines, including granulocyte‐macrophage colony stimulating factor (GM‐CSF). GM‐CSF is also overexpressed in the airways of symptomatic asthmatics. Objectives To examine the early effects of systemic corticosteroids on cytokine expression, we investigated whether ex vivo synthesis of GM‐CSF is suppressed in the bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMCs) of normal and mild allergic asthmatic subjects obtained 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 normal subjects (n = 9) 4 h after an intravenous bolus dose of 80 mg prednisolone, and cultured for 0–18 h in the presence or absence of lipopolysaccharide (LPS; 10 μg/mL). Enzyme immunoassay was used to assess GM‐CSF levels in BAL cell and PBMC culture supernatants, and in BAL fluid. Results After placebo, GM‐CSF synthesis tended to be higher in BAL cells from asthmatics than in normals. LPS stimulation significantly increased median (interquartile range) GM‐CSF synthesis by BAL cells ex vivo from 16.4 (23 to 74) to 35.8 (3–148) pg/106 cells in normals (P