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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1989 Mar;75(3):451–456.

The effect of cyclosporin A in delaying maturation of the small intestine during weaning in the rat.

A G Cummins 1, J T Labrooy 1, D J Shearman 1
PMCID: PMC1541942  PMID: 2702783

Abstract

As maturation of the small intestine has similar features to an immunologically mediated reaction, we studied the effect of the immunosuppressive agent, cyclosporin A (CyA), on the development of the small intestine during weaning in the DA x PVG rat. Intestinal development was measured by villus area, crypt length, crypt cell production rate (CCPR), and disaccharidase activity. Rat pups received either cyclosporin A (7.5 mg/kg daily subcutaneously) or polyethoxylated castor oil (Cremophor, drug vehicle) subcutaneously from 12 days of age. Cremophor- and CyA-treated litters were killed at 18, 20, 22, 24, and 26 days of age. CyA-treated animals had retarded weight gain, lower mesenteric lymph node and spleen weights, fewer intraepithelial lymphocytes, and reduced systemic secretion of rat mucosal mast cell protease II. CyA treatment retarded any increase in villus area, crypt length and CCPR until day 26 of age. Lactase activity was retained longer, and sucrase and maltase induction was delayed. We conclude that CyA retarded normal development of the small intestine, but some maturation still occurred at the end of weaning.

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Selected References

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  1. ABRAMS G. D., BAUER H., SPRINZ H. Influence of the normal flora on mucosal morphology and cellular renewal in the ileum. A comparison of germ-free and conventional mice. Lab Invest. 1963 Mar;12:355–364. [PubMed] [Google Scholar]
  2. Alarcon P., Lebenthal E., Lee P. C. Effect of difluoromethyl ornithine (DFMO) on small intestine of adult and weanling rats. Dig Dis Sci. 1987 Aug;32(8):883–888. doi: 10.1007/BF01296713. [DOI] [PubMed] [Google Scholar]
  3. Babický A., Parízek J., Ostádalová I., Kolár J. Initial solid food intake and growth of young rats in nests of different sizes. Physiol Bohemoslov. 1973;22(6):557–566. [PubMed] [Google Scholar]
  4. Beer A. E., Billingham R. E. Immunologic benefits and hazards of milk in maternal-perinatal relationship. Ann Intern Med. 1975 Dec;83(6):865–871. doi: 10.7326/0003-4819-83-6-865. [DOI] [PubMed] [Google Scholar]
  5. Cummins A. G., Munro G. H., Ferguson A. Effect of cyclosporin A on rat mucosal mast cells and the associated protease RMCPII. Clin Exp Immunol. 1988 Apr;72(1):136–140. [PMC free article] [PubMed] [Google Scholar]
  6. Cummins A. G., Steele T. W., LaBrooy J. T., Shearman D. J. Maturation of the rat small intestine at weaning: changes in epithelial cell kinetics, bacterial flora, and mucosal immune activity. Gut. 1988 Dec;29(12):1672–1679. doi: 10.1136/gut.29.12.1672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ferguson A., Jarrett E. E. Hypersensitivity reactions in small intestine. I Thymus dependence of experimental 'partial villous atrophy'. Gut. 1975 Feb;16(2):114–117. doi: 10.1136/gut.16.2.114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ferguson A., Parrott D. M. Growth and development of "antigen-free" grafts of foetal mouse intestine. J Pathol. 1972 Feb;106(2):95–101. doi: 10.1002/path.1711060205. [DOI] [PubMed] [Google Scholar]
  9. Harper J. F. Peritz' F test: basic program of a robust multiple comparison test for statistical analysis of all differences among group means. Comput Biol Med. 1984;14(4):437–445. doi: 10.1016/0010-4825(84)90044-1. [DOI] [PubMed] [Google Scholar]
  10. Herbst J. J., Sunshine P., Kretchmer N. Intestinal malabsorption in infancy and childhood. Adv Pediatr. 1969;16:11–64. [PubMed] [Google Scholar]
  11. Herbst J. J., Sunshine P. Postnatal development of the small intestine of the rat. Changes in mucosal morphology at weaning. Pediatr Res. 1969 Jan;3(1):27–33. doi: 10.1203/00006450-196901000-00004. [DOI] [PubMed] [Google Scholar]
  12. Klein R. M., McKenzie J. C. The role of cell renewal in the ontogeny of the intestine. II. Regulation of cell proliferation in adult, fetal, and neonatal intestine. J Pediatr Gastroenterol Nutr. 1983 May;2(2):204–228. [PubMed] [Google Scholar]
  13. Lebenthal E., Sunshine P., Kretchmer N. Effect of carbohydrate and corticosteroids on activity of -glucosidases in intestine of the infant rat. J Clin Invest. 1972 May;51(5):1244–1250. doi: 10.1172/JCI106919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lee P. C., Lebenthal E. Early weanling and precocious development of small intestine in rats: genetic, dietary or hormonal control. Pediatr Res. 1983 Aug;17(8):645–650. doi: 10.1203/00006450-198308000-00008. [DOI] [PubMed] [Google Scholar]
  15. Lund E. K., Bruce M. G., Smith M. W., Ferguson A. Selective effects of graft-versus-host reaction on disaccharidase expression by mouse jejunal enterocytes. Clin Sci (Lond) 1986 Aug;71(2):189–198. doi: 10.1042/cs0710189. [DOI] [PubMed] [Google Scholar]
  16. MacDonald T. T., Spencer J. Evidence that activated mucosal T cells play a role in the pathogenesis of enteropathy in human small intestine. J Exp Med. 1988 Apr 1;167(4):1341–1349. doi: 10.1084/jem.167.4.1341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mayrhofer G., Fisher R. Mast cells in severely T-cell depleted rats and the response to infestation with Nippostrongylus brasiliensis. Immunology. 1979 May;37(1):145–155. [PMC free article] [PubMed] [Google Scholar]
  18. Mowat A. M., Ferguson A. Intraepithelial lymphocyte count and crypt hyperplasia measure the mucosal component of the graft-versus-host reaction in mouse small intestine. Gastroenterology. 1982 Aug;83(2):417–423. [PubMed] [Google Scholar]
  19. Thomson A. W., Webster L. M. The influence of cyclosporin A on cell-mediated immunity. Clin Exp Immunol. 1988 Mar;71(3):369–376. [PMC free article] [PubMed] [Google Scholar]
  20. Wright N. A. The experimental analysis of changes in proliferative and morphological status in studies on the intestine. Scand J Gastroenterol Suppl. 1982;74:3–10. [PubMed] [Google Scholar]

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