Prednisone administration alters basal and endotoxin-stimulated expression of adhesion molecules on human neutrophils

The objective of this study was to determine if glucocorticoid (GC) suppression of neutrophil recruitment responses to bacterial-derived agents is mediated in part by alterations in the adhesion phenotype of circulating neutrophils. We examined basal and bacterial lipopolysaccharide (LPS)-stimulated expression of β2 integrins, L-selectin and the P-selectin ligand PSGL-1 on human whole blood neutrophils from 5 subjects before and 1 hr after administration of prednisone (60 mg followed 24 hrs later by 30 mg). Prior to prednisone (i.e., control), incubation of heparinized human whole blood with LPS (30 min, 37°C) resulted in concentration dependent increases in expression of CD11b and CD18, and shedding of L-selectin and PSGL-1 on neutrophils, with a maximal response seen at 10 ng/ml. Administration of two oral doses of prednisone resulted in a significant decrease in basal expression of L-selectin (mean fluorescence intensity (MFI) control 52.5±6.3 vs. prednisone 35.4±2.3, p<0.05) and a trend toward decreased CD11b expression (MFI of control 59.4±9.8 vs. prednisone 44.5±4.1), with no decrease in CD18 or PSGL-1 expression. LPS-induced (10 ng/ml) (MFI control 110.5±17.2 vs prednisone 78.4±2.2, p<0.05), while upregulation of CD11b in response to PMA was not affected (MFI 128.8±11.5 control vs. 131.6±11.3 prednisone). Similarly, LPS-induced upregulation of CD18 was decreased (MFI 50.2±6.6 control vs. 38.1±1.8 prednisone), while PMA-induced upregulation of CD18 was unaffected. Shedding of L-selectin and PSGL-1 was not inhibited by prednisone, and prednisone did not alter expression of the LPS receptor CD14. These data indicate that oral GC may alter leukocyte recruitment by decreasing basal and LPS-stimulated neutrophil adhesion molecule expression.