Abstract
BackgroundThere appears to be a significant increase in the prevalence rate of autism. Reasons for the increase are unknown, however, there is a substantial body of evidence that suggests the etiology involves infections of the pregnant mother or of a young child. Most infections result in fever that is routinely controlled with antipyretics such as acetaminophen. The blocking of fever inhibits processes that evolved over millions of years to protect against microbial attack. Immune mechanisms in the central nervous system are part of this protective process.HypothesisThe blockage of fever with antipyretics interferes with normal immunological development in the brain leading to neurodevelopmental disorders such as autism in certain genetically and immunologically disposed individuals.Testing the hypothesisEpidemiological studies to determine associations between the use of antipyretics and neurodevelopmental disorders should be undertaken. Biochemical tests will involve the examination of fluids/serum by mass spectrometry and the determination of cytokine/chemokine levels in serum and cell culture fluids after stimulation with fever-inducing molecules from bacteria, viruses and yeast. Postmortem brain can be examined by immunohistochemistry or other methods such as fluorescent in situ hybridization (FISH) to determine altered expression levels of chemokines/cytokines and other molecules.Implications of the hypothesis1) The use of antipyretics during pregnancy or in young children may be reserved for more severe fevers. 2) The perplexing genetic findings in autism may be better understood by categorizing genes along functional pathways. 3) New treatments based on immune, cell, pharmacological or even heat therapies may be developed.
Highlights
There appears to be a significant increase in the prevalence rate of autism
Little is known about the etiology, and the diagnosis of autism is done by behavioral criteria as no biomarkers have yet been identified
Aspirin is not currently recommended in the pediatric population due to an association with Reye's syndrome [53]
Summary
Autism, a neurodevelopmental disorder, is increasing in the pediatric population [1]. These studies suggest that the AP directly affects immune cells and is not a secondary response to AP-hepatitis The premise of this theory is that the blockage of fever with antipyretics interferes with normal immunological development in the brain, leading to neurodevelopmental disorders in certain genetically and immunologically disposed individuals. 2) Peripheral blood cells from subjects with neurodevelopmental disorders and controls can be examined in culture for chemokine/cytokine production after stimulation with bacterial, viral, or yeast PAMPs. The incubation of isolated white blood cells with bacterial or viral components (LPS, unmethylated DNA, dsRNA) that are known to increase cytokine expression may be useful to determine if there are genetically encoded differences in cells from subjects with autism and age- and sex-matched controls. These treatments may be based on immune, cell, pharmacological or even heat therapies that alter the CNS immune system
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