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.

Scientists studied pregnant mice with thyroid problems to understand how this affects their babies' brain development and behavior. They found that babies had low levels of a protective immune chemical (IL-10) in early life, followed by high levels of inflammatory chemicals later. When they gave the baby mice IL-10 supplements during the first critical weeks, it prevented autism-like behaviors from developing. This research suggests that immune system problems very early in life might contribute to autism.

This preclinical study examined how maternal hypothyroidism affects inflammatory markers in offspring mouse brains and their relationship to autism-like behaviors. Researchers tracked five key cytokines in the prefrontal cortex from embryonic development through early adulthood. The study found that IL-10 (an anti-inflammatory cytokine) decreased significantly in early postnatal life (P3-P10), while pro-inflammatory cytokines (IL-6, IL-17A, IL-1β, TNF-α) increased later (P14 onwards). When researchers administered IL-10 supplements during the critical early period (P3-P10), it normalized all cytokine levels and significantly reduced autism-like behaviors.

This suggests early immune dysregulation may contribute to autism development and that targeted anti-inflammatory intervention during specific developmental windows could be therapeutic.

Suggests early postnatal period may be critical for immune intervention in autism. IL-10 supplementation shows promise as therapeutic approach. Findings support investigating maternal thyroid function and early immune markers as potential risk factors and intervention targets in human autism research.

Animal model study limiting direct human translation. Sample sizes not reported. Single intervention approach tested. Unclear if behavioral improvements persist long-term beyond P42 assessment.

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. 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. 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. 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.