Interleukin-2 and the Septohippocampal System: Intrinsic Actions and Autoimmune Processes Relevant to Neuropsychiatric Disorders

Abstract

The effects of IL-2 on brain development, function, and disease are the result of IL-2's actions in the peripheral immune system and its intrinsic actions in the central nervous system (CNS). Determining whether, and under what circumstances (e.g., development, acute injury), these different actions of IL-2 are operative in the brain is essential to make significant advances in understanding the multifaceted affects of IL-2 on CNS function and disease, including psychiatric disorders. For several decades, there has been a great deal of speculation about the role of autoimmunity in brain disease. More recently, we have learned a great deal about the role of cytokines on neurobiological processes, and there have been many studies that have found peripheral immune alterations in patients with neurological and neuropsychiatric diseases. Despite a plethora of published literature, almost all of this data in humans is correlative and much of the basic research has understandably relied on simpler models (e.g., in vitro models). Good animal models such as our IL-2 knockout mouse model could provide valuable new insight into understanding how the complex biology of a cytokine such as IL-2 can have simultaneous, dynamic effects on multiple systems (e.g., regulating homeostasis in the brain and immune system, autoimmunity that can affect both systems). Animal models can also provide much needed new data elucidating neuroimmunological and autoimmune processes involved in brain development and disease. Such information may ultimately provide critical new insight into the role of brain cytokines and autoimmunity in prominent neurological and neuropsychiatric diseases (e.g., Alzheimer's disease, autism, multiple sclerosis, schizophrenia).

Altered IL-2, IL-6 and IL-8 serum levels in schizophrenia patients with tardive dyskinesia

“…Therefore, there may exist close relationship between the IL-2, dopaminergic dysfunction and TD symptom in schizophrenia patients. Furthermore, IL-2 could lead to the autoimmune responses of neurons (Petitto et al, 2012a) and subsequently affect neuronal function and produce neuroinflammation (Song et al, 1999). For example, (McAfoose andBaune, 2009) and(de Araujo et al, 2009) reported that IL-2 increased survival and synaptogenesis of dopaminergic neurons during development.…”

Altered Cytokine and BDNF Levels in Autism Spectrum Disorder

“…Ancillary to the primary purpose, it found also that serum BDNF was elevated significantly in the ASD patients compared with healthy controls. Several brain disorders, associated with alterations of the normal mechanisms controlling development, have been associated with specific variants of cytokines and/or their receptors (Angelidou et al 2012;Petitto et al 2012;Vezzani and Friedman 2011). Cytokines may originate from peripheral immune cells and reach the CNS by crossing the blood-brain barrier or may be produced directly within the CNS by neurons and glial cells.…”

Assessment of the natural killer cell, IFN-ƒ× and IL-10 blood levels in children with attention-deficit/hyperactivity disorder

“…20 Many studies have shown that people with neuropsychiatric illnesses have impaired peripheral immune systems, and there is currently a lot of knowledge on the involvement of cytokines in brain processes. 21 There was a significantly lower IL-10 blood level in children with ADHD compared to the normal controls. A previous study by Cortese et al, 2019, 22 showed a significant negative correlation between IL-10 and ADHD symptoms.…”