# IL-6 Inhibition Partially Ameliorates Maternal Immune Activation-Induced Autism-Like Behavioral Abnormalities in Mice

**Authors:** Xiaoyun Zhang, Weili Luo, Kaiyue He, Yuping Li, Yan Chen, Zhipeng Xu, Zi-Kai Zhou

PMC · DOI: 10.3390/cimb47100852 · Current Issues in Molecular Biology · 2025-10-16

## TL;DR

This study shows that blocking IL-6 can reduce some autism-like behaviors in mice caused by maternal immune activation during pregnancy.

## Contribution

The study demonstrates that IL-6 inhibition partially reverses social and anxiety-related behavioral deficits in a mouse model of maternal immune activation.

## Key findings

- IL-6 inhibition reduced anxiety-like behaviors in MIA offspring.
- Social interaction deficits were partially restored by IL-6 inhibition.
- Core ASD-like features like social preference and repetitive behaviors remained unaffected.

## Abstract

Prenatal maternal immune activation (MIA) has been implicated in autism spectrum disorder (ASD) pathogenesis, with interleukin-6 (IL-6) identified as a key inflammatory mediator. We investigated the therapeutic potential of IL-6 inhibition in an MIA mouse model induced by Toxoplasma gondii soluble tachyzoite antigen (STAg). Adult MIA offspring received systemic administration of the IL-6-neutralizing antibody (MP5-20F3) or isotype control, followed by behavioral assessments one week later. Open field and elevated plus maze tests revealed heightened anxiety-like behaviors in the STAg offspring, which were largely reversed by IL-6 inhibition. Reciprocal social interaction tests showed diminished sociability in the STAg offspring, which was partially restored by IL-6 inhibition. However, core ASD-like features, including impaired social preference and recognition in the three-chamber test, as well as increased repetitive behaviors, remained resistant to IL-6 inhibition. These findings demonstrate that STAg-induced MIA elicits anxiety-like and ASD-like phenotypes in adult offspring, with IL-6 playing an important role in anxiety-like behaviors and social interaction deficits. Systemic IL-6 inhibition partially ameliorates behavioral abnormalities. This study suggests that IL-6-targeted therapies may address a subset of ASD-related symptoms, and comprehensive strategies are needed for broader efficacy.

## Linked entities

- **Proteins:** IL6 (interleukin 6)
- **Diseases:** autism spectrum disorder (MONDO:0005258)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}
- **Diseases:** inflammatory (MESH:D007249), impaired (MESH:D060825), social interaction (MESH:C563663), Autism (MESH:D001321), Behavioral Abnormalities (MESH:D001523), ASD (MESH:D000067877), anxiety (MESH:D001007)
- **Chemicals:** MP5-20F3 (-)
- **Species:** Toxoplasma gondii (species) [taxon 5811], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12564645/full.md

## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC12564645/full.md

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Source: https://tomesphere.com/paper/PMC12564645