A single intravenous dose of prednisolone induces phosphatidylserine externalization, loss of surface marker expression and a 24-h net increase in human peripheral blood lymphocytes ex vivo.
To understand how corticosteroids act; a characterization of their effects on lymphocytes is necessary. The effect of in vivo corticosteroids on lymphocyte subpopulations, their surface molecules and externalization of phosphatidylserine (apoptosis) is examined. In a crossover study, a single, intravenous dose of 2 mg/kg prednisolone or saline was given to six male adult human volunteers. Blood samples were withdrawn before and 30 min, 2, 5, 23 and 29 h thereafter. Lymphocyte subsets were determined by FACS analysis. Externalization of phosphatidylserine was measured by Annexin-V; cell fragments were excluded by propidium iodide staining. Lymphocyte number decreased from 2,007 +/- 473 to 634 +/- 119 microl after 5 h and rose to 3,112 +/- 436 microl after 23 h. CD4, CD8 and B cell counts declined significantly after 5 h (P < or = 0.01). The expression of CD28 or CD95 on T cells and the natural killer cells were unaffected. There was a significant rebound of lymphocyte numbers above baseline 23 h after prednisolone. At baseline 9.9 +/- 3.8% of cells in the lymphocyte gate did not stain for CD3, CD20 or CD56 (referred to as "null cells"). 5 h after application of prednisolone, there was a significant increase of "null cells" (28 +/- 12%, P = 0.018). The percentage of phosphatidylserine positive CD4 cells rose from 8.1 +/- 3.3 to 19.8 +/- 8% after intravenous prednisolone, while the percentage of phosphatidylserine positive CD8, B and NK cells remained largely unchanged. Prednisolone induces a most significant depletion of CD4 cells, which to some degree is associated with apoptosis. The net increase of lymphocyte numbers 23 h after prednisolone application may be a beneficial late effect of a single i.v. prednisolone shot.
Jetzek-Zader
Martin
M
Department of Anaesthesiology, UKD, Heinrich Heine University, Düsseldorf, Germany.
Gudowius
Sonja
S
Feyen
Oliver
O
Stevens
Markus
M
Lipfert
Peter
P
Niehues
Tim
T
D000328:Adult; D000954:Antigens, Surface / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018592:Cross-Over Studies; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007275:Injections, Intravenous; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000139:chemically induced / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010718:Phosphatidylserines / Q000378:metabolism*; D011239:Prednisolone / Q000008:administration & dosage*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000954:Antigens, Surface; D005938:Glucocorticoids; D010718:Phosphatidylserines; D011239:Prednisolone