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Updated: Jun 10, 2026
07:08
Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Delayed developmental immunotoxicity of prenatal benzodiazepines
M Schlumpf1, E E Bütikofer, A A Schreiber
1Institute of Pharmacology, University of Zürich, Zürich, Switzerland.
Summary
Prenatal exposure to benzodiazepines (BDZ) in rats alters offspring immune responses, affecting cytokine production like TNF-alpha and IL-6 long-term. These changes suggest an interaction with peripheral benzodiazepine receptors (PBR) impacting immune development.
Area of Science:
- Immunology
- Neuroscience
- Developmental Biology
Background:
- Classical benzodiazepines (BDZ) and peripheral benzodiazepine receptor (PBR) agonists administered to pregnant rats during critical gestational periods can impair offspring immune function.
- Previous studies indicate a long-lasting depression of cellular and humoral immune responses in offspring following prenatal BDZ exposure.
Purpose of the Study:
- To investigate the effects of prenatal diazepam exposure on mitogen-stimulated cytokine production in rat offspring.
- To explore the potential involvement of peripheral benzodiazepine receptors (PBR) in mediating these immune alterations.
Main Methods:
- Pregnant rats were treated with low-dose diazepam or a PBR agonist between gestational days 14-20.
- Offspring immune responses, including splenocyte cytokine production (TNF-alpha, IL-6, IL-1, IL-2), prostaglandin E(2) (PGE(2)), and interferon-gamma (IFN-gamma), were assessed at various ages.
- Peripheral benzodiazepine receptor (PBR) characteristics were evaluated using [(3)H]PK 11195 binding assays.
Main Results:
- Prenatal diazepam exposure significantly altered cytokine profiles in offspring, with reduced TNF-alpha and IL-6 at 2 and 8 weeks, and differential effects on IL-1 based on sex and age.
- T-cell derived IL-2 was decreased postnatally but normalized in adulthood.
- Prostaglandin E(2) levels were increased and interferon-gamma levels were decreased in young offspring, with persistent alterations into adulthood.
- Altered PBR binding characteristics (B(max) and Kd) were observed in offspring, suggesting drug-receptor interactions.
Conclusions:
- Prenatal exposure to benzodiazepines induces lasting changes in the developing immune system of rats, particularly in cytokine production.
- The observed immune alterations and modified PBR characteristics suggest that PBR may play a role in mediating the effects of prenatal BDZ exposure on immune development.
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