Expression and release of the monocyte lipopolysaccharide receptor antigen CD14 are suppressed by glucocorticoids in vivo and in vitro.

Abstract

The effect of glucocorticoid (GC) treatment on expression and release of the monocyte cell surface LPS receptor Ag CD14 was studied in vivo and in vitro. In patients with acute inflammatory diseases receiving GC pulse therapy serum concentrations of soluble CD14 and CD14 expression by peripheral blood monocytes decreased significantly. The LPS-binding capacity correlated positively with the amount of cell surface CD14 by human blood monocytes. In vitro, a time- and dose-dependent effect of GC preparations on monocyte membrane and soluble CD14 by cultured peripheral blood monocytes was found. Incubation with 2 x 10(-8) M prednisolone down-regulated cell surface CD14 after 72 h, and 2 x 10(-7) M suppressed CD14 expression even after 24 h. Prednisolone also decreased release of the soluble CD14 Ag, where a 10-fold higher GC concentration was required for a significant suppression compared with membrane CD14 during culture. Expression of other monocyte membrane Ags were either unchanged (CD33, CD35), diminished (CD13, CD89), or increased (CD32) by GC, indicating no general down-modulation of cell surface Ag expression. Preincubation with glucocorticoids for 24 h significantly down-regulated CD14 expression during subsequent steroid-free culture for at least 7 days. In cultured monocytes, the LPS-induced increase of membrane and soluble CD14 was markedly but not completely inhibited by prednisolone. Therefore, GC treatment suppresses the up-regulation of the LPS receptor during endotoxin challenge, and likewise, the IL-1 secretion after LPS stimulus was significantly diminished. Taken together, the suppression of the monocytic cell surface and soluble endotoxin receptor CD14 by GC may contribute to the increased risk of infections in patients undergoing steroid therapy.

• Authors: W A Nockher, J E Scherberich
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 158 Issue 3 Pg. 1345-52 (Feb 01 1997) ISSN: 0022-1767 [Print] United States
• PMID: 9013978 (Publication Type: Journal Article)

Chemical References

• Antigens, Differentiation, Myelomonocytic
• Glucocorticoids
• Immunosuppressive Agents
• Interleukin-1
• Lipopolysaccharide Receptors
• Lipopolysaccharides

Topics

• Adult
• Antigens, Differentiation, Myelomonocytic (metabolism)
• Cell Membrane (metabolism)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Female
• Glucocorticoids (pharmacology)
• Humans
• Immunosuppressive Agents (pharmacology)
• Interleukin-1 (metabolism)
• Lipopolysaccharide Receptors (metabolism)
• Lipopolysaccharides (metabolism, pharmacology)
• Male
• Middle Aged
• Monocytes (metabolism)
• Solubility
• Time Factors