Developmental immunotoxicity investigations in the SD rat following pre- and post-natal exposure to cyclosporin
Article first published online: 25 OCT 2006
© 2006 Wiley-Liss, Inc.
Birth Defects Research Part B: Developmental and Reproductive Toxicology
Volume 77, Issue 5, pages 430–437, October 2006
How to Cite
Barrow, P. C., Horand, F. and Ravel, G. (2006), Developmental immunotoxicity investigations in the SD rat following pre- and post-natal exposure to cyclosporin. Birth Defects Research Part B: Developmental and Reproductive Toxicology, 77: 430–437. doi: 10.1002/bdrb.20093
- Issue published online: 25 OCT 2006
- Article first published online: 25 OCT 2006
- Manuscript Accepted: 10 AUG 2006
- Manuscript Received: 7 AUG 2006
- developmental toxicity;
BACKGROUND: The development and function of the immune system was assessed in juvenile SD rats following pre- or post-natal exposure to cyclosporin. The main objective was to assess the feasibility of the methods available for the detection of adverse effects on the development of the immune system for use in the safety assessment of medicines. METHODS: In a pre-natal experiment, 15 pregnant rats were given 10 mg/kg/day of cyclosporin by gavage from day 6 of gestation until 4 days after parturition. A control group received olive oil. In a post-natal experiment, the pups from 35 litters were given 10 mg/kg/day of cyclosporin by gavage from 4 to 28 days of age. Half of the pups in each litter were given water and acted as controls. Immune endpoints were determined in the pups in both experiments from two to 10 weeks of age, including: lymphocyte subsets, serum immunoglobulin titres, serum autoantibodies, primary antibody response to sheep red blood cells (SRBC), delayed-type hypersensitivity response, humoral response to keyhole limpet haemocyanin, spleen cellularity, immune organ weights, and histopathology. RESULTS: Pre-natal exposure caused no effects on immune function. Post-natal exposure caused immune depression during the treatment period and a persistent impairment of the immune system characterised by lymphoid hyperplasia in the spleen and a reduced primary antibody response to SRBC at 10 weeks of age. CONCLUSIONS: These results demonstrate the importance of a post-treatment follow-up period in developmental immunotoxicity studies, in order to distinguish between the transient effects of immune modulation and the persistent consequences of developmental toxicity. Birth Defects Research (Part B) 77:430–437, 2006. © 2006 Wley-Liss, Inc.