Jump to main content
US EPA
United States Environmental Protection Agency
Search
Search
Main menu
Environmental Topics
Laws & Regulations
About EPA
Health & Environmental Research Online (HERO)
Contact Us
Print
Feedback
Export to File
Search:
This record has one attached file:
Add More Files
Attach File(s):
Display Name for File*:
Save
Citation
Tags
HERO ID
4092899
Reference Type
Journal Article
Title
Developmental Immunotoxicity Of Dexamethasone And Cyclosporin A
Author(s)
Tegelenbosch, MM; Waalkens-Berendsen, ID; Wolterbeek, AP; Dijkstra, A; Kuper, FC; Van Zijverden, M; Koerkamp, EI; Van den Berg, PT; Penninks, AH
Year
2005
Is Peer Reviewed?
1
Journal
Reproductive Toxicology
ISSN:
0890-6238
EISSN:
1873-1708
Report Number
DART/TER/5001507
Volume
Oct
Issue
3
Language
English
Abstract
Introduction: As pre- and postnatal exposure can result in various types of immunotoxic effects in the offspring, incorporation of immunotoxicological determinations is considered in reproductive toxicology studies. The impact of maternal treatment and direct dosing of pre-weaning rats with dexamethasone and cyclosporin A on development of the immune system was investigated. Materials and methods: Two developmental toxicity studies were performed in Wistar rats. In the first study mated rats were treated subcutaneously with 20 or 100 ug dexamethasone/ kg/bw from gestation day (GD) 0 to postnatal day (PND) 21. In the second study, dams were treated by gavage with 5 or 15mg cyclosporin A/kg/bw from GD 6 to PND 21 and a selection of pups, derived from control- and high dose group dams, was dosed directly with 12.5 mg cyclosporin A/kg from PND 14 and #150;20. Next to enhanced immunopathology (weight and pathology of various lymphoid organs and lymphocyte subset analyses in blood) at various points of time, the function of the immune system was studied by the T cell-dependent antibody response to Keyhole Limpet Hemocyanine (KLH). At least five male and five female pups were selected for each determination. The KLH-specific antibodies were measured by ELISA in blood collected 7 days after the pups were injected intraveneously with 250 ug KLH around PND 21 and 70. Results: Dexamethasone induced maternal toxicity, decreased pup weights from the 100 g dexamethasone/kg treated dams and slight immunopathological effects on thymus, spleen, bone marrow and mesenteric lymph nodes at PND 4 and 21. The KLH-specific IgM and IgG antibody titers measured at PND 21 and PND 70 were not affected. Cyclosporin A induced a dose related increased post-implantation loss. If only the dams were exposed to cyclosporin A from GD 6 to PND 21 no effects were seen on the pup weight gain or on microscopical examinations of the various lymphoid organs. Moreover, no effects were seen on lymphocyte subset analysis in pups at PND 21 and PND 70 and the KLH-specific IgM and IgG titers. The KLHspecific IgM antibody titer measured in pups additionally dosed directly with cyclosporin A from PND 14 and #150;20 was slightly increased (as compared to non-treated pups). The increase was similar in pups dosed directly originating from cyclosporin-treated dams and control dams. Conclusion: These data suggest that maternal dexamethasone and cyclosporin A treatment up to dose levels of 100 ug/kg and 15 mg/kg, respectively, which are expected to induce immunotoxicity in the dams, hardly affected the measured postnatal immune system-related parameters in the offspring at PND 4, 21, 30 and 70. Additional exposure of the pre-weaning rat (directly dosed) may be a more appropriate model for investigating possible effects on the development of the immune system.
Home
Learn about HERO
Using HERO
Search HERO
Projects in HERO
Risk Assessment
Transparency & Integrity