Developmental immunotoxicity of dexamethasone: comparison of fetal versus adult exposures.
Dexamethasone-21 phosphate was administered (s.c.) to pregnant CD rats at days 6-21 of gestation (0, 0.0625, 0.125, 0.25, and 0.5 mg/kg/day) with identical exposure of non-pregnant adult females. Some reproductive (anogenital distance) and growth (body weight) measures of pups were altered. In the juvenile (5 weeks), the delayed type hypersensitivity response to KLH was significantly reduced at all doses examined and this pattern continued into adulthood (13 weeks). In contrast, the DTH response of adults exposed to DEX was unaltered even at the highest dose. Few DEX-induced changes were seen in offspring or adult blood parameters or in splenocytes analyzed for cell surface makers (by flow cytometry). The thymus of both exposed pups (both ages) and adults showed a marked reduction in the medulla/lobe area beginning with the 0.125 mg/kg/day DEX exposure level. Macrophage production of TNF and NO was only marginally affected as was splenocyte production of IL-4 and IFN-gamma. In contrast, pups assessed as juveniles were significantly depressed in splenic IL-2 and IL-10 production. DEX exposure altered serum antibody levels across age groups with an increase of KLH-specific IgG (beginning with the 0.0125 mg/kg/day dose) while total IgE was reduced. These results suggest that while DEX exposure produces some common alterations following in utero versus adult exposure, fetal exposure (even at the lowest doses tested) produces marked and persistent functional loss (DTH) not evident in exposed adults. Furthermore, there was no apparent advantage in delaying immune assessment until the offspring reached adulthood.
Dietert
Rodney R
RR
Department of Microbiology and Immunology, College of Veterinary Medicine, Veterinary Medical Center, C5-135 VMC, Tower Rd, Cornell University, Ithaca, NY 14853, USA. rrd1@cornell.edu
Lee
Ji-Eun
JE
Olsen
John
J
Fitch
Kevin
K
Marsh
James A
JA
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003907:Dexamethasone / Q000031:analogs & derivatives* / Q000633:toxicity*; D004342:Drug Hypersensitivity / Q000196:embryology / Q000276:immunology*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000196:embryology / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D009929:Organ Size / Q000187:drug effects / Q000276:immunology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology
D016207:Cytokines; C004180:dexamethasone 21-phosphate; D007073:Immunoglobulin E; D003907:Dexamethasone