IL-4 increases GABAergic phenotype in rat retinal cell cultures: involvement of muscarinic receptors and protein kinase C

Sholl‐Franco, Alfred; Marques, Patrı́cia M.B; Ferreira, Cecı́lia M.C; Araújo, Elizabeth Giestal de

doi:10.1016/s0165-5728(02)00327-2

Cited by 20 publications

(11 citation statements)

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“…It is involved in shaping the adaptive immune response, and is often associated with parasite defense, asthma, and atopy. IL-4 has been shown to impact neuronal proliferation, differentiation, survival, and synapse formation(55-58). Elevated IL-4 has also been linked to ASD with increased levels reported in maternal serum during the second trimester of pregnancy(59), and in amniotic fluid (60) collected from mothers giving birth to a child later diagnosed with ASD.…”

Section: Discussionmentioning

confidence: 99%

Neonatal Cytokine Profiles Associated With Autism Spectrum Disorder

Krakowiak

Goines

Tancredi

et al. 2017

Biological Psychiatry

193

134

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Background Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that can be reliably diagnosed as early as 24 months. Immunological phenomena, including skewed cytokine production, have been observed among children with ASD. Little is known about whether immune dysregulation is present before diagnosis of ASD. Methods We utilized neonatal blood spots from 214 children with ASD (141 severe, 73 mild/moderate), 62 typically developing (TD), and 27 developmental delayed controls who participated in CHARGE (Childhood Autism Risks from Genetics and the Environment), a population-based case-control study. Levels of 17 cytokines/chemokines were compared across groups and in relation to developmental/behavioral domains. Results Interleukin (IL)-1β and IL-4 were independently associated with ASD vs. TD although these relationships varied by ASD symptom intensity. Elevated IL-4 associated with increased odds of severe ASD (ASDsev) (odds ratio[OR]=1.40, 95% confidence interval[CI] 1.03, 1.91) whereas IL-1β associated with increased odds of mild/moderate ASD (ASDmild) (OR=3.02, 95% CI 1.43, 6.38). Additionally, IL-4 was associated with a higher likelihood of ASDsev vs. ASDmild (OR=1.35, 95% CI 1.04, 1.75). In male ASD cases, IL-4 was negatively associated with non-verbal cognitive ability (β=−3.63, SE=1.33, P=0.04). Conclusions This study is part of a growing effort to identify early biological markers for ASD. We demonstrate that peripheral cytokine profiles at birth are associated with ASD later in childhood and that cytokine profiles vary depending on ASD severity. Cytokines have complex roles in neurodevelopment, and dysregulated levels may be indicative of genetic differences and environmental exposures or their interactions that relate to ASD.

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Section: Discussionmentioning

confidence: 99%

Neonatal Cytokine Profiles Associated With Autism Spectrum Disorder

Krakowiak

Goines

Tancredi

et al. 2017

Biological Psychiatry

193

134

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“…IL-4 influences retinal circuitry by regulating progenitor cell proliferation and differentiation (da Silva, Campello-Costa et al 2008). During later phases of neurodevelopment, IL-4 can alter synapse formation; increasing the proportion of GABAergic synapses in cell culture models (Sholl-Franco, Marques et al 2002). …”

Section: Cytokines In Asdmentioning

confidence: 99%

Cytokine dysregulation in autism spectrum disorders (ASD): Possible role of the environment

Goines

Ashwood

2013

Neurotoxicology and Teratology

252

177

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Autism spectrum disorders (ASD) are neurodevelopmental diseases that affect an alarming number of individuals. The etiological basis of ASD is unclear, and evidence suggests it involves both genetic and environmental factors. There are many reports of cytokine imbalances in ASD. These imbalances could have a pathogenic role, or they may be markers of underlying genetic and environmental influences. Cytokines act primarily as mediators of immunological activity, but they also have significant interactions with the nervous system. They participate in normal neural development and function, and inappropriate activity can have a variety of neurological implications. It is therefore possible that cytokine dysregulation contributes directly to neural dysfunction in ASD. Further, cytokine profiles change dramatically in the face of infection, disease, and toxic exposures. Therefore, imbalances may represent an immune response to environmental contributors to ASD. The following review is presented in two main parts. First, we discuss select cytokines implicated in ASD, including IL-1Β, IL-6, IL-4, IFN-γ, and TGF-Β, and focus on their role in the nervous system. Second, we explore several neurotoxic environmental factors that may be involved in the disorders, and focus on their immunological impacts. This review represents an emerging model that recognizes the importance of both genetic and environmental factors in ASD etiology. We propose that the immune system provides critical clues regarding the nature of the gene by environment interactions that underlie ASD pathophysiology.

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“…Several lines of evidence have demonstrated that in some cases cytokines, IL-4 and IL-10, may be neuroprotective through anti-inflammatory effects (Spera et al, 1998;Dietrich et al, 1999;Sholl-Franco et al, 2002;Abraham et al, 2004). Moreover, the effects of cytokines such as IL-4, IL-10, and IFN-γ may confer protection against pro-inflammatory substances released from MP (FIG.…”

Section: Had Therapeuticsmentioning

confidence: 99%

Mononuclear phagocytes in the pathogenesis of neurodegenerative diseases

et al. 2005

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Brain mononuclear phagocytes (MP, bone marrow monocyte-derived macrophages, perivascular macrophages, and microglia) function to protect the nervous system by acting as debris scavengers, killers of microbial pathogens, and regulators of immune responses. MP are activated by a variety of environmental cues and such inflammatory responses elicit cell injury and death in the nervous system. MP immunoregulatory responses include secretion of neurotoxic factors, mobilization of adaptive immunity, and cell chemotaxis. This incites tissue remodelling and blood-brain barrier dysfunction. As disease progresses, MP secretions engage neighboring cells in a vicious cycle of autocrine and paracrine amplification of inflammation leading to tissue injury and ultimately destruction. Such pathogenic processes tilt the balance between the relative production of neurotrophic and neurotoxic factors and to disease progression. The ultimate effects that brain MP play in disease revolves "principally" around their roles in neurodegeneration. Importantly, common functions of brain MP in neuroimmunity link highly divergent diseases (for example, human immunodeficiency virus type-one associated dementia, Alzheimer's disease and Parkinson's disease). Research into this process from our own laboratories and those of others seek to harness MP inflammatory processes with the intent of developing therapeutic interventions that block neurodegenerative processes and improve the quality of life in affected people.

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IL-4 increases GABAergic phenotype in rat retinal cell cultures: involvement of muscarinic receptors and protein kinase C

Cited by 20 publications

References 50 publications

Neonatal Cytokine Profiles Associated With Autism Spectrum Disorder

Neonatal Cytokine Profiles Associated With Autism Spectrum Disorder

Cytokine dysregulation in autism spectrum disorders (ASD): Possible role of the environment

Mononuclear phagocytes in the pathogenesis of neurodegenerative diseases

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