Some cytokines of interest in autism [87]
| Cytokine | Function | References |
|---|---|---|
| IL-1β | IL-1β is an inflammatory cytokine expressed very early in immune responses. It propagates tissue inflammation by activating local immune cells and the vascular endothelium. IL-1β also stimulates IL-6 production. IL-1β can cross the blood-brain interface and stimulate its own expression in the hypothalamus, resulting in altered neuroendocrine activity including fever and sickness behavior. IL-1 and its receptors are found throughout the nervous system during critical developmental periods. It appears to have a role in both central nervous system (CNS) pathology and healing. | [69, 87–97] |
| IL-4 | IL-4 is a cytokine that activates Janus kinase/signal transducer and activator of transcription (JAK/STAT; STAT6), mitogen-activated protein kinase (MAPK), and phosphoinositide 3 (PI3) kinase signaling pathways. It induces “alternatively activated macrophages that promote tissue repair, activate basophils and mast cells, and promote B-cell isotype switching towards IgG1 and IgE. IL-4 also participates in the antihelminth immune response by inducing gut epithelial cell turnover. In addition, it plays a role in allergy and asthma-related immune responses. During brain development, IL-4 promotes the formation of oligodendrocytes among neuronal progenitor cells. In later stages of neurodevelopment, IL-4 alters the formation of synapses, leading to an increase in the proportion of gamma-aminobutyric acid (GABAergic) synapses in cell cultures. | [70, 87, 98–107] |
| IFN-γ | IFN-γ is a type II produced primarily by T cells and NK cells during cell-mediated immune responses. Its main function is to activate macrophages and participate in the immune response against viral infections. It also signals through the JAK/STAT (STAT1) and MAPK pathways. IFN-γ and IL-4 offset each other’s activity through Th1/Th2 interactions, so a dysfunction/imbalance in one cytokine often affects the other. IFN-γ also influences dendritic morphology and synaptogenesis, resulting in long-term changes in neuronal connectivity and communication. | [87, 108–116] |
| TGF-β | TGF-β is a superfamily of proteins that includes growth differentiation factors, bone morphogenic proteins (BMPs), activins, and inhibins. They function to maintain immune homeostasis, direct lymphocyte differentiation, and orchestrate aspects of embryonic development. They exist in three isoforms, each with overlapping roles. TGF-β1 is largely immune-suppressive, limiting excessive T cell activity and inflammation. It is also involved in neuronal migration, survival, and synaptogenesis. | [117–120] |
All authors contributed to the conception of this study. SO performed the database search and wrote the first draft of the manuscript; DAL contributed to sections of the manuscript including the conceptualization and drawing of Figure 1. All authors contributed to manuscript revision, read and approved the submitted version.
The authors declare that they have no conflicts of interest.
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SO received partial support from the National Institute of Environmental Health Sciences (NIEHS) award RO1ES025584 to DAL. The funders had no role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript.
© The Author(s) 2022.