Reduced IL-10 in the early postnatal period contributes to pro-inflammatory phenotype and autism-like behavior in offspring mice induced by maternal hypothyroidism during pregnancy.

OBJECTIVE

To investigate the dynamic changes of five key cytokines in the prefrontal cortex of offspring from maternal hypothyroidism at different developmental time points and further identify potentially critical cytokines based on the magnitude and timing of their alterations.

METHODS

Pregnant C57BL/6J mice were rendered hypothyroid with 0.2 g/L methimazole in drinking water from gestational day 9 to postnatal day 10 (GD9-P10). Two experiments were conducted: 1. dynamic profiling of IL-10, IL-6, IL-17A, IL-1β, and TNF-α in the medial prefrontal cortex of offspring at E15/17/19 and P0/3/7/14/21/42; 2. intraperitoneal IL-10 (100 ng/kg) or saline administered to offspring from P3 to P10, followed by cytokine assays and behavioral tests at P21 and P42.

RESULTS

IL-10 levels in the model group fell significantly at P3 and remained low till P10, whereas IL-6, IL-17A, IL-1β, and TNF-α rose synchronously from P14. Exogenous IL-10 administration restored all cytokines to control levels and markedly ameliorated autism-like behaviors in offspring.

CONCLUSION

The reduction in IL-10 may represent the earliest cytokine alteration, which may be involved in mediation of autism-like phenotypes after maternal hypothyroidism; early postnatal IL-10 supplementation may serve as an effective approach to re-establish anti-inflammatory homeostasis and alleviate behavioral abnormalities, providing a novel time window and molecular target for immune-based intervention in ASD.