Abstract.
Background: Glucocorticoids acting as anti-inflammatory or immunosuppressive drugs have been shown to exert most of their effects genomically. Recent findings suggest that non-genomic activity might be relatively more important in mediating the therapeutic effects of high-dose pulsed glucocorticoid. However, few non-genomic anti-inflammatory effects were reported, much less non-genomic mechanisms.
Objective: This study was performed to investigate the nongenomic effects of glucocorticoids on human neutrophil degranulation.
Methods: Purified human neutrophils were pretreated with 6 α-methylprednisolone or hydrocortisone for 5 min, and then primed with N-formyl-methionyl-leucyl-phenylalanine (fMLP) (10−6 M) or phorbol myristate acetate (PMA) (50 ng/ml) in the presence of cytochalasin B. The release of two markers of neutrophil granules, lactoferrin and myeloperoxidase, was measured by ELISA and enzymology methods respectively.
Results: Both 6 α-methylprednisolone (10−5–10−4 M) and hydrocortisone (10−4 M) showed significant inhibitory effects on neutrophil degranulation within 5 min after fMLP administration. For PMA stimulated degranulation, 6 α-methylprednisolone (10−4 M) showed significant inhibitory effects (p < 0.01), while hydrocortisone (10−4 M) only showed an inhibitory tendency (P > 0.05). Neither RU486 (10−5 M) nor cycloheximide (10−4 M) could alter the inhibitory effects of glucocorticoids.
Conclusion: Our results demonstrate that megadoses of glucocorticoids exert rapid inhibitory effects on human neutrophil degranulation at the cellular level via a new mechanism that is independent of corticosteroid type II receptor occupation or protein synthesis. We infer that these effects may be very important when glucocorticoids act as anti-inflammatory drugs during pulse therapy.
Article PDF
Similar content being viewed by others
Author information
Authors and Affiliations
Corresponding author
Additional information
Received 20 May 2004; returned for revision 21 July 2004; accepted by M.J. Parnham 23 September 2004
L. Liu and Y. X. Wang contributed equally to this work.
Rights and permissions
About this article
Cite this article
Liu, L., Wang, Y.X., Zhou, J. et al. Rapid non-genomic inhibitory effects of glucocorticoids on human neutrophil degranulation. Inflamm. res. 54, 37–41 (2005). https://doi.org/10.1007/s00011-004-1320-y
Issue Date:
DOI: https://doi.org/10.1007/s00011-004-1320-y