Dexamethasone inhibits maturation and alters function of monocyte-derived dendritic cells from cord blood.
Critically ill infants are treated with dexamethasone (Dx) and other glucocorticoids to reduce inflammation and to promote lung and cardiac function. The neonatal immune system is immature, so neonatal dendritic cells (DCs) might be especially sensitive to glucocorticoid-mediated immunosuppression. To test this, we compared Dx treatment of monocyte-derived DCs from cord (CB) and adult blood (AB). Dx decreased CD1a levels on both AB and CB DCs. CB-treated cells also exhibited decreased expression of CD83 and increased expression of CD14, alterations not observed in AB DCs. Characteristic immature endocytic activity was sustained and enhanced in Dx-treated CB DCs, whereas AB DCs matured normally. Maintenance of endocytosis corresponded with CD14 expression. Dx markedly increased CB DC IL-10, a T cell helper 2 (Th2)-preferential cytokine, while reducing IL-12, a counterbalancing Th1 cytokine. AB DCs were also affected, but increases in IL-10 and decreases in IL-12 were more modest. Dx treatment also inhibited DC-induced T cell proliferation, but CB DCs were inhibited more. In short, neonatal DCs seemed to be especially sensitive to the immunosuppressive effects of Dx as indicated by altered phenotype, endocytic function, ability to stimulate T cells, and cytokine shift favoring Th2. These alterations in DC function are consistent with an increased risk for certain infections and atopic diseases.
Mainali
Elsie S
ES
Department of Pediatrics, VA Commomnwealth University Health System, Richmond, VA 23298, USA. emainali@hsc.vsc.edu
Kikuchi
Takeshi
T
Tew
John G
JG
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015703:Antigens, CD; D001249:Asthma / Q000473:pathology; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D003907:Dexamethasone / Q000494:pharmacology*; D004705:Endocytosis; D005312:Fetal Blood / Q000166:cytology*; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D012306:Risk; D013601:T-Lymphocytes / Q000378:metabolism; D018418:Th2 Cells; D000097802:CD83 Antigen
D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D016207:Cytokines; D003907:Dexamethasone; D005938:Glucocorticoids; D007136:Immunoglobulins; D007166:Immunosuppressive Agents; D016753:Interleukin-10; D018664:Interleukin-12; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen