Interleukin‐4 as a Neuromodulatory Cytokine

Sholl‐Franco, Alfred; Silva, Ana Gabriela Ledo Santos da; Adão-Novaes, Juliana

doi:10.1111/j.1749-6632.2008.03962.x

Cited by 13 publications

(5 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is upregulated during CNS inflammation, inducing alternative activation of glial cells and protecting from apoptosis (Garg, Kipnis et al 2009; Sholl-Franco, da Silva et al 2009; You, Luo et al 2011). In a mouse model for Alzheimer’s disease, IL-4 can attenuate disease progression (Kiyota, Okuyama et al 2010).…”

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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…Interleukin-4 (IL-4) is well-known anti-inflammatory cytokine and has diverse immunomodulatory functions on cell repair and regeneration in the central nervous system [14,15]. In the context of neuroinflammation under pathological conditions, it exerts either harmful or beneficial effects on neurons by regulating oxidative stress in vivo and in vitro [9,11,[15][16][17]. Thus, the present study examined whether pKr-2-induced neurotoxicity could contribute to endogenous production of IL-4, which is neurotoxic or neuroprotective in hippocampus in vivo.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-4-Mediated Oxidative Stress Is Harmful to Hippocampal Neurons of Prothrombin Kringle-2-Lesioned Rat In Vivo

2020

View full text Add to dashboard Cite

The present study investigated the effects of reactive microglia/macrophages-derived interleukin-4 (IL-4) on hippocampal neurons in prothrombin kringle-2 (pKr-2)-lesioned rats. pKr-2 was unilaterally injected into hippocampus in the absence or presence of IL-4 neutralizing antibody (IL-4Nab). Immunohistochemical analysis showed a significant loss of Nissl+ and NeuN+ cells and activation of microglia/macrophages (increase in reactive OX-42+ and OX-6+ cells) in the hippocampus at 7 days after pKr-2 injection. The levels of IL-4 expression were upregulated in the reactive OX-42+ microglia/macrophages as early as 1 day, maximal at 3 days and maintained up to 7 days after pKr-2 injection. Treatment with IL-4Nab significantly increased neuronal survival in pKr-2-treated CA1 layer of hippocampus in vivo. Accompanying neuroprotection, IL-4 neutralization inhibited activation of microglia/macrophages, reactive oxygen species-derived oxidative damages, production of myeloperoxidase- and inducible nitric oxide synthase-derived reactive nitrogen species and nitrosative damages as analyzed by immunohistochemistry and hydroethidine histochemistry. These results suggest that endogenous IL-4 expressed on reactive microglia/macrophages mediates oxidative/nitrosative stress and play a critical role on neurodegeneration of hippocampal CA1 layer in vivo.

show abstract

“…IL-4 is an anti-inflammatory cytokine with neuroprotective, nutritive and immunosuppressive effects ( 8 ), which can induce M2 macrophages to produce opioid peptides. Through activating peripheral opioid receptors, mechanical hypersensitivity caused by neuropathy and pain will be relieved ( 9 ).…”

Section: Discussionmentioning

confidence: 99%

Study on the correlation between IL-12p70, IL-17A and migraine in children

Yang,

Liu,

Liu

et al. 2024

Front. Neurol.

View full text Add to dashboard Cite

ObjectiveTo compare the serum levels of 12 cytokines in migraine group, encephalitis with headache symptoms group, pneumonia without headache symptoms group and migraine subgroups to explore the cytokines associated with migraine in children and their levels.MethodsA total of 44 children with migraine, 27 children in the encephalitis group with headache symptoms and 44 children in the pneumonia group without headache symptoms were selected from January 2022 to August 2023 in Hebei Children’s Hospital. They were all tested for serum cytokines by immunofluorescence assay. The migraine group was further divided into subgroups according to different age, gender, course of disease, and presence of coinfection. The differences of serum cytokine levels among the above groups were compared, and the correlation analysis was carried out.ResultsExcept IL-5, there were no significant differences in the expression levels of other 11 inflammatory cytokines between migraine subgroups. Compared with encephalitis with headache symptoms group and pneumonia without headache symptoms group the serum levels of IL-4, TNF-α, IL-17A, and IL-12p70 were higher in migraine group than in pneumonia group, and the levels of IL-12p70 were higher than those in encephalitis group (p < 0.05). An increase in serum IL-12p70 (OR = 1.267, 95%CI 1.054–1.523, p = 0.012) and IL-17A (OR = 1.066, 95%CI 1.016–1.119, p = 0.010) levels had a significant effect on migraine.ConclusionElevated serum levels of IL-12p70 and IL-17A may increase the risk of migraine in children, which has certain diagnostic and predictive value.

show abstract

Interleukin‐4 as a Neuromodulatory Cytokine

Cited by 13 publications

References 101 publications

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

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

Interleukin-4-Mediated Oxidative Stress Is Harmful to Hippocampal Neurons of Prothrombin Kringle-2-Lesioned Rat In Vivo

Study on the correlation between IL-12p70, IL-17A and migraine in children

Contact Info

Product

Resources

About