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 alpha-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 alpha-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 alpha-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.
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 alpha-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 alpha-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 alpha-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.
Authors: D M H Cavalcanti; C M C Lotufo; P Borelli; Z S Ferreira; R P Markus; S H P Farsky Journal: Br J Pharmacol Date: 2007-11-05 Impact factor: 8.739
Authors: Jennifer R Rainville; Grant L Weiss; Nathan Evanson; James P Herman; Nandini Vasudevan; Jeffrey G Tasker Journal: Steroids Date: 2017-12-12 Impact factor: 2.668
Authors: Justin A Green; Chau T H Tran; Jeremy J Farrar; Mai T H Nguyen; Phu H Nguyen; Sinh X Dinh; Nghia D T Ho; Chuong V Ly; Hien T Tran; Jon S Friedland; Guy E Thwaites Journal: PLoS One Date: 2009-09-30 Impact factor: 3.240