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Effect of prenatal steroid treatment on the developing immune system

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Abstract

Prenatal steroids have an undisputed positive effect of decreasing neonatal morbidity and mortality by improving fetal lung maturation. Some concerns have been raised on long-term consequences on the hypothalamic–pituitary–adrenal axis and cognition, but there are no studies addressing effects on the immune system. The thymus is an essential organ for the development and selection of T cells, and thymocytes are extremely sensitive to steroids. Using a mouse model for prenatal steroid administration, we show here that betamethasone treatment to the mother has a profound effect on the thymus of the offspring. We find the thymus volume reduced, affecting mostly the developing CD4+ CD8+ double-positive thymocytes and a compensatory accelerated transition of the earlier stages to replenish the depleted compartment. This effect lasts for at least 3 days, which correspond to a very relevant period for the selection of the T cell repertoire. Moreover, we show that low doses of betamethasone have similar effects on human thymocytes in vitro. Therefore, further studies are needed to analyze possible long-term consequences of this treatment on the immune system of the offspring.

Key message

  • Betamethasone administered to the mother before birth reaches the fetal thymus.

  • Prenatal betamethasone results in massive loss of developing thymocytes.

  • The effects of betamethasone on thymus development are visible for several days.

  • Human thymocytes are also sensitive to low doses of betamethasone.

  • Altered thymocyte development around birth may have an effect on the immune system.

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Acknowledgments

We would like to thank the Flow Cytometry Core Facility at the UKE, Tobias Mummert, Thomas Andreas, and Corinna Kulicke for excellent technical help. This project is supported by the Excellence Initiative of the Hamburg Research Foundation (LEXI).

Conflict of interest

The authors reported no potential conflicts of interest.

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Authors and Affiliations

  1. Department of Immunology, University Medical Center Hamburg-Eppendorf, Martinistrasse, 52-20246, Hamburg, Germany

    Ines Diepenbruck, Manuela Kolster & Eva Tolosa

  2. Diagnostic and Interventional Radiology Department, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Chressen C. Much

  3. Institute of Doping Analysis and Sports Biochemistry, Kreischa, Germany

    Aniko Krumbholz & Detlef Thieme

  4. Laboratory for Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    René Thieme, M. Emilia Solano & Petra C. Arck

  5. CHIESI GmbH, Hamburg, Germany

    Silke Diepenbruck

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  1. Ines Diepenbruck
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  2. Chressen C. Much
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  3. Aniko Krumbholz
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  4. Manuela Kolster
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  10. Eva Tolosa
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Correspondence to Eva Tolosa.

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Diepenbruck, I., Much, C.C., Krumbholz, A. et al. Effect of prenatal steroid treatment on the developing immune system. J Mol Med 91, 1293–1302 (2013). https://doi.org/10.1007/s00109-013-1069-2

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  • DOI: https://doi.org/10.1007/s00109-013-1069-2

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