Alzheimer Patients Treated With an AchE Inhibitor Show Higher IL-4 and Lower IL-1β Levels and Expression in Peripheral Blood Mononuclear Cells

Gambi, Francesco; Reale, Marcella; Iarlori, Carla; Salone, Anatolia; Toma, Lucia; Paladini, Carlo; Luca, Giovanna De; Feliciani, Claudio; Salvatore, Mirella; Salerno, Rosa Maria; Theoharides, Theoharis C.; Conti, Pio; Exton, Michael S.; Gambi, D.

doi:10.1097/01.jcp.0000125683.74595.2f

Cited by 52 publications

(38 citation statements)

References 77 publications

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“…AChEIs may possibly contribute in delaying disease progression by interfering in the delicate balance of the cytokine cascade. 69 Our data demonstrated that both RS and RL exerted significant improvement of cognitive effect, decrease in plasma CRP, Hcy, and ADMA, downregulation of BACE1, AChE, and IL1B gene expression and decreased AChE activity as compared to AlCl 3 -treated animals. The overcoming effect of RL compared to RS was manifested by normalization of cognitive effect as assessed by MWM (Figure 4), gene expression ( Figure 5), and AChE activity (Table 4).…”

mentioning

confidence: 70%

Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer's disease

Ismail¹,

ElMeshad²,

Salem³

2013

IJN

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Background:To sustain the effect of rivastigmine, a hydrophilic cholinesterase inhibitor, nanobased formulations were prepared. The efficacy of the prepared rivastigmine liposomes (RLs) in comparison to rivastigmine solution (RS) was assessed in an aluminium chloride (AlCl 3 )-induced Alzheimer's model. Methods: Liposomes were prepared by lipid hydration (F1) and heating (F2) methods. Rats were treated with either RS or RLs (1 mg/kg/day) concomitantly with AlCl 3 (50 mg/kg/day). Results:The study showed that the F1 method produced smaller liposomes (67.51 ± 14.2 nm) than F2 (528.7 ± 15.5 nm), but both entrapped the same amount of the drug (92.1% ± 1.4%). After 6 hours, 74.2% ± 1.5% and 60.8% ± 2.3% of rivastigmine were released from F1 and F2, respectively. Both RLs and RS improved the deterioration of spatial memory induced by AlCl 3 , with RLs having a superior effect. Further biochemical measurements proved that RS and RLs were able to lower plasma C-reactive protein, homocysteine and asymmetric dimethylarginine levels. RS significantly attenuated acetylcholinesterase (AChE) activity, whereas Na + / K + -adenosine triphosphatase (ATPase) activity was enhanced compared to the AlCl 3 -treated animals; however, RLs succeeded in normalization of AChE and NaGene-expression profile showed that cotreatment with RS to AlCl 3 -treated rats succeeded in exerting significant decreases in BACE1, AChE, and IL1B gene expression. Normalization of the expression of the aforementioned genes was achieved by coadministration of RLs to AlCl 3 -treated rats. The profound therapeutic effect of RLs over RS was evidenced by nearly preventing amyloid plaque formation, as shown in the histopathological examination of rat brain. Conclusion: RLs could be a potential drug-delivery system for ameliorating Alzheimer's disease.

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confidence: 70%

Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer's disease

Ismail¹,

ElMeshad²,

Salem³

2013

IJN

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“…Furthermore, it is proved that induction of IL-4 production reduces A deposition and attenuates AD pathogenesis in different transgenic mice (Kijota et al, 2010;Kawahara et al, 2012). In fact, several studies proposed that amelioration of AD pathology in patients treated with acetylcholinesterase inhibitors is due to increased IL-4 expression Gambi et al, 2004), supporting a pivotal immunomodulatory effect of IL-4 in AD.…”

Section: Introductionmentioning

confidence: 99%

Metabolomic research on the role of interleukin-4 in Alzheimer’s disease

et al. 2015

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Abstract:Inflammation plays a prominent role in the pathogenesis of Alzheimer's disease, affecting both brain and the peripheral system. Thus, modulation of inflammation in animal models of this neurodegenerative disorder may be of great interest to elucidate the pathological mechanisms underlying this inflammatory component. To this end, a metabolomic investigation on a triple transgenic mouse model obtained by crossing the APP/PS1 mice with interleukin-4 knockout mice (a model of impaired immune function) was performed for the first time. Serum samples from transgenic mice and wild type animals were analyzed by direct infusion mass spectrometry followed by multivariate statistics in order to identify altered metabolites. Subsequently, metabolic pathway analysis allowed the elucidation of potential pathological mechanisms associated with the development of Alzheimer-type disorders in response to interleukin-4 deficiency, such as impaired homeostasis of histamine, altered metabolism of amino acids (threonine, aspartate and tyrosine), deregulated urea cycle and increased production of eicosanoids. Therefore, this work demonstrates the potential of this triple transgenic model with modulated immunity for the study of pathological mechanisms associated with inflammation in Alzheimer's disease. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation COMMENTS FOR THE AUTHOR:Reviewer #1: The authors have not included some important requests for clarification to be added to the manuscript by the reviewer therefor another minor revision is required. Abstract still poorly writtenFor example this sentence:Thereby, the investigation of this inflammatory component presents a great potential for the elucidation of pathological mechanisms underlying to disease, the discovery of potential markers of diagnosis and the development of novel therapeutic approaches Abstract was rewritten. Authors commentWe did not use internal standards because we considered that the validation of reproducibility in metabolomic methods is better assessed using QC samples. In this sense, Naz et al. recently described that "although spiking some selected metabolites could give a good approach to the general behaviour of the method, results cannot be assumed for all the components in the sample" (J Chromatogr A 2014;1353:99). Instead, biological QCs show a similar composition to real samples, so they are preferable for validating non-targeted approaches. Thus, "the se of QCs in non-targeted metabolomics analysis can be considered as equivalent to the use of standards in routine target analysis". Reviewer comment: I don't agree with this statement how can you account for a one off issue and internal standards are also in the sample matrix. You need add this justification to the manuscriptInternal standards must present similar physico-chemical properties to the chemical species of interest in the sample. However, metabolomics approaches are not focused on individual compounds, so the use of internal standards in these method...

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“…IL-4 is expressed in normal brains [15] and appears to be affected by cholinesterase inhibitors [16] . Two studies found that IL-4 levels in peripheral monocytes of AD patients treated with donepezil were significantly higher than the levels in untreated AD patients and non-demented controls [17,18] . Furthermore, IL-1 ␤ levels were significantly lower in donepezil-treated AD patients [17] , and these changes were independent of age, gender, and other comorbidities [18] .…”

Section: Interleukin Familymentioning

confidence: 99%

Peripheral Cytokines and Chemokines in Alzheimer’s Disease

Lee

Chung²,

Choi³

et al. 2009

Dement Geriatr Cogn Disord

125

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A chronic inflammatory process has been implicated in the neuropathology of Alzheimer’s disease (AD). The present review focuses on the current knowledge of circulating serum and plasma biomarkers of AD that are linked to inflammatory reactions. There is abundant evidence that inflammatory mechanisms within the central nervous system contribute to cognitive impairment via cytokine-mediated interactions between neurons and glial cells. Interleukins 1, 4, 6, 10, 12, 16, and 18, tumour necrosis factor, and several chemokines have been suggested as biomarkers of AD. Nonetheless, data on circulating cytokine levels are somewhat inconsistent with regard to peripheral cytokine dysregulation in AD. In summary, definite statements concerning differences in inflammatory biomarkers between controls and AD patients will require the use of sensitive multiplex assays in large patient groups in conjunction with measures of disease severity.

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Alzheimer Patients Treated With an AchE Inhibitor Show Higher IL-4 and Lower IL-1β Levels and Expression in Peripheral Blood Mononuclear Cells

Cited by 52 publications

References 77 publications

Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer's disease

Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer's disease

Metabolomic research on the role of interleukin-4 in Alzheimer’s disease

Peripheral Cytokines and Chemokines in Alzheimer’s Disease

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Alzheimer Patients Treated With an AchE Inhibitor Show Higher IL-4 and Lower IL-1β Levels and Expression in Peripheral Blood Mononuclear Cells

Cited by 52 publications

References 77 publications

Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer&#39;s disease

Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer&#39;s disease

Metabolomic research on the role of interleukin-4 in Alzheimer’s disease

Peripheral Cytokines and Chemokines in Alzheimer’s Disease

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Product

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Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer's disease

Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer's disease