Summary: Researchers are investigating why fever can temporarily improve autism symptoms so they can recreate the beneficial effect without causing fever. Their work focuses on the immune signaling molecule IL-17a and aims to translate animal findings into safe, targeted therapies.
Building on animal studies that point to immune-to-brain signaling as a driver of the so-called “fever effect,” the team plans to create a biobank of clinical samples to compare immune responses in people with and without autism. The goal is to identify molecular and cellular markers that could guide new treatment approaches.
Key Facts:
- Fever Effect: Some people with autism spectrum disorder (ASD) experience temporary improvements in behavior and social interaction during infections that produce fever, motivating research into its mechanisms.
- Immune Focus: The immune cytokine IL-17a has emerged as a crucial mediator in animal models, appearing to modulate brain circuits linked to sociability and repetitive behaviors.
- Therapy Development: Researchers aim to leverage the biological mechanisms behind the fever effect to develop therapies that reproduce its benefits without inducing fever.
Source: MIT
Researchers are following decades of caregiver reports that some individuals with autism experience clearer social engagement and reduced repetitive behaviors during febrile illnesses.
Supported by two new grants from The Marcus Foundation totaling $2.1 million over three years, investigators at MIT and Harvard Medical School are studying how immune activity associated with infection can transiently alter autism-related behaviors. The project is led by Gloria Choi, associate professor at The Picower Institute for Learning and Memory and the Department of Brain and Cognitive Sciences at MIT, in collaboration with Jun Huh, associate professor of immunology at Harvard Medical School.
“The fever effect isn’t caused solely by higher body temperature, but the phenomenon is real and offers a promising path to develop therapies that mitigate ASD symptoms,” Choi said. Huh added, “To my knowledge, this is among the only naturally occurring situations where developmentally established autism traits show marked, though temporary, improvement.”
The Marcus Foundation has funded autism research for more than 30 years, supporting projects that span awareness, diagnostics and treatment development. Bernie Marcus, founder and chairman of the foundation, said he hopes the new awards will accelerate translation of this research into meaningful clinical advances.
Brain-immune interplay in autism
Choi and Huh’s decade-long collaboration has mapped a connection between maternal infection, immune signaling and neurodevelopmental outcomes in offspring. In mouse models, maternal infection during pregnancy—shaped in part by the mother’s gut microbiome—can cause neurodevelopmental changes that resemble autism, including decreased sociability.
Their work has identified IL-17a, an immune-signaling cytokine, as a key mediator. Elevated maternal IL-17a acts on its receptors in the fetal brain and can increase activity in a cortical area called S1DZ, which is linked to social behavior. In some models, maternal infection also primes offspring immune cells to produce more IL-17a in later life.
A 2020 study from the same teams demonstrated that mice with autism-like traits caused by maternal infection showed improved social behavior when they experienced infections themselves—mirroring anecdotal reports from people with ASD. The researchers found that overexpression of IL-17a during those infections appeared to calm affected brain circuits. Direct intracerebral delivery of IL-17a also produced behavioral improvement in mice whose mothers had not been infected, suggesting the cytokine itself can be sufficient to modify circuit function.
From mice to people: new studies and a biobank
These findings led to a central question: can the protective or restorative mechanisms activated during fever be harnessed to produce lasting therapeutic benefit? To answer that, Choi and Huh will continue dissecting the molecular, cellular and neural circuit cascade triggered by IL-17a and related immune signals in mice, tracking how those signals reduce repetitive behaviors and improve sociability.
Concurrently, the team will establish a human biobank containing blood plasma and stool samples from volunteers with autism who do and do not report fever-associated improvements, alongside matched volunteers without autism. By cataloging cytokines, immune cell states, microbiome features and other biomarkers, the researchers aim to define the biological signature of the fever effect in people.
If distinct cellular and molecular features correlate with clinical improvements during fever, those signatures could point to drug targets or immune-modulating strategies that mimic the beneficial response without requiring an actual infection or elevated temperature. Detailed mapping of how immune signals act on specific brain cells and circuits will inform the design of therapies intended to reproduce the fever effect safely and effectively.
“Understanding the precise mechanisms behind fever-associated improvements will allow us to recreate those effects therapeutically, potentially for individuals who never experience them naturally,” Choi said. Huh remarked, “We hope this work will be a first step toward uncovering the biological underpinnings of fever responses and, ultimately, toward novel interventions that improve the lives of people with ASD and their families.”
About this Autism research news
Author: David Orenstein
Source: MIT
Contact: David Orenstein – MIT
Image: The image is credited to Neuroscience News