Interleukin-18 produced by peripheral blood cells is increased in Alzheimer’s disease and correlates with cognitive impairment

Bossù, Paola; Ciaramella, Antonio; Salani, Francesca; Bizzoni, Federica; Varsi, Erika; Iulio, Fulvia Di; Giubilei, Franco; Gianni, Walter; Trequattrini, Alberto; Moro, Maria Luisa; Bernardini, Sergio; Caltagirone, Carlo; Spalletta, Gianfranco

doi:10.1016/j.bbi.2007.10.001

Cited by 93 publications

(64 citation statements)

References 20 publications

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“…In addition to its pro-inflammatory activity, IL-18 is involved in aging and neurodegeneration [99]. Elevated expression of IL-18 has been detected in AD brains [100], and peripheral cells from AD patients show increased production of IL-18 upon stimulation [35]. Gene association analysis further supports the involvement of IL-18 in AD development.…”

Section: Other Pro-inflammatory Cytokinesmentioning

confidence: 85%

“…Meanwhile, the C allele of IL-18 -607 and the CC genotype are associated with increased AD risk in Han Chinese and Italian Caucasian populations, respectively [33,34]. Functional analyses have revealed that the IL-18 -607 CC genotype results in significantly elevated IL-18 production by blood mononuclear cells in AD patients [35], implying that this polymorphism exacerbates AD processes via the promotion of IL-18 secretion. However, negative interactions have also been found in Italian Caucasians by Segat et al [101], implying that this interaction needs to be confirmed in further studies with larger numbers of AD patients.…”

Section: Other Pro-inflammatory Cytokinesmentioning

confidence: 99%

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Inflammatory Cytokines and Alzheimer’s Disease: A Review from the Perspective of Genetic Polymorphisms

2016

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Neuroinflammatory processes are a central feature of Alzheimer's disease (AD) in which microglia are over-activated, resulting in the increased production of proinflammatory cytokines. Moreover, deficiencies in the antiinflammatory system may also contribute to neuroinflammation. Recently, advanced methods for the analysis of genetic polymorphisms have further supported the relationship between neuroinflammatory factors and AD risk because a series of polymorphisms in inflammation-related genes have been shown to be associated with AD. In this review, we summarize the polymorphisms of both pro-and anti-inflammatory cytokines related to AD, primarily interleukin-1 (IL-1), IL-6, tumor necrosis factor alpha, IL-4, IL-10, and transforming growth factor beta, as well as their functional activity in AD pathology. Exploration of the relationship between inflammatory cytokine polymorphisms and AD risk may facilitate our understanding of AD pathogenesis and contribute to improved treatment strategies.

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Section: Other Pro-inflammatory Cytokinesmentioning

confidence: 85%

Section: Other Pro-inflammatory Cytokinesmentioning

confidence: 99%

Inflammatory Cytokines and Alzheimer’s Disease: A Review from the Perspective of Genetic Polymorphisms

2016

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“…Its engagement promotes Th1 polarization with a consequent activation of an inflammatory immune response. Interestingly, ICAM-1 expression on DCs is striking upregulated by pro-inflammatory stimuli such as IL-18 [24], a cytokine which appears to be significantly increased in AD patients both at brain [25] and peripheral blood cell levels [22]. In general, ICAM-1 is considered a pro-inflammatory molecule and since neurodegenerative diseases, like multiple sclerosis or Parkinson's disease, are associated with a considerable degree of neuroinflammation, it is not surprising that ICAM-1 is aberrantly hyperexpressed by glial cells of patients affected by these diseases [26,27].…”

Section: Discussionmentioning

confidence: 99%

“…As previously described [22], PBMCs were freshly isolated from heparinized venous blood by centrifugation on density gradient (Lympholyte-H, Cederlane, Hornby, Canada). Then 2 × 10 6 PBMCs, suspended in 0.…”

Section: Cellsmentioning

confidence: 99%

Increased Pro-Inflammatory Response by Dendritic Cells from Patients with Alzheimer's Disease

Ciaramella

Bizzoni

Salani

et al. 2010

JAD

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Abstract. Alzheimer's disease (AD) is characterized by abnormal accumulation of amyloid-β peptide (Aβ) into extracellular fibrillar deposits, paralleled by chronic neuroinflammatory processes. Although Aβ seems to be causative in AD brain damage, the role of the immune system and its mechanisms still remain to be clarified. We have recently shown that normal monocyte-derived dendritic cells (MDDCs), when differentiated in the presence of Aβ1−42, acquire an inflammatory phenotype and a reduced antigen presenting ability. Here we studied MDDCs derived from AD patients in comparison with MDDCs obtained from healthy control subjects (HC). MDDCs from AD patients, at variance with HC-derived cells, were characterized by an augmented cell recovery, a consistent increase in the expression of the pro-inflammatory ICAM-1 molecule, a decrease in the expression of the co-stimulatory CD40 molecule, and an impaired ability to induce T cell proliferation. Furthermore, MDDCs from AD produced higher amounts of IL-6 than HC-derived cells, confirming the more pronounced pro-inflammatory features of these cells in AD patients. Consistent results have been also obtained with monocytes, the MDDC precursors. In fact, while unstimulated monocytes do not appear to be different in AD and HC, after stimulation with lipopolysaccharide, AD monocytes overexpressed ICAM-1 with respect to controls, suggesting that common pathways of monocyte activation and MDDC differentiation are altered in AD. Overall, these findings show that AD-linked dysregulated immune mechanisms exist, which lead to dendritic cell-mediated over-activation of inflammation and impaired antigen presentation, thus supporting the view that immune cell activation could play an important role in AD pathogenesis.

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“…Similarly, the -607C>A promoter variant disrupts the binding site for a cAMP-responsive protein. IL-18 variants have been associated with various chronic infl ammatory conditions and viral diseases, such as hepatitis B 16 and Alzheimer's disease 17,18 .…”

Section: Introductionmentioning

confidence: 99%

Impact of the IL-18 gene polymorphism in response to antiviral therapy in chronic HCV genotype 4 patients

Mandour

Nemr

Kishk

et al. 2014

Rev. Soc. Bras. Med. Trop.

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Introduction: Interleukin (IL)-18 is a well-known major proinfl ammatory cytokine with broad biological effects. The major immunomodulatory functions of IL-18 include enhancing T cell and natural killer cell cytotoxicity. Serum levels of this cytokine were shown to increase in chronic hepatitis C patients compared to non-infected healthy people. An association between IL-18 gene promoter polymorphisms and pegylated interferon (PEG-IFN) and ribavirin treatment outcomes has been reported for individuals with chronic hepatitis C virus genotype 1 (HCV-1). In this study, HCV genotype 4 (HCV-4) patients were assessed for IL-18 gene polymorphisms and treatment outcomes or severity of liver disease because data concerning the impact of IL-18 gene polymorphisms on patients with HCV-4 infections are limited. Methods: This study included 123 chronic HCV-4 Egyptian patients and 123 apparently healthy volunteer blood donors who served as a control group. HCV genotyping was performed using the line probe assay. IL-18 genotyping was performed using the TaqMan Real-Time PCR method in all 246 patient and control samples. Results: In our study, all patients had HCV-4. IL-18 gene single nucleotide polymorphism (SNP) (-607C/A) genotype distributions and allele frequencies did not differ between HCV patients and normal healthy subjects or between patient groups when compared according to the therapeutic response. Moreover, the presence of an IL-18 SNP was not associated with histological disease severity. We conclude that the presence of the IL-18 SNP rs1946518 does not affect the outcome of chronic HCV-4 treatment in Egyptian patients. Conclusions: The IL-18 SNP rs1946518 does not affect response to treatment in chronic HCV-4 patients.

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Interleukin-18 produced by peripheral blood cells is increased in Alzheimer’s disease and correlates with cognitive impairment

Cited by 93 publications

References 20 publications

Inflammatory Cytokines and Alzheimer’s Disease: A Review from the Perspective of Genetic Polymorphisms

Inflammatory Cytokines and Alzheimer’s Disease: A Review from the Perspective of Genetic Polymorphisms

Increased Pro-Inflammatory Response by Dendritic Cells from Patients with Alzheimer's Disease

Impact of the IL-18 gene polymorphism in response to antiviral therapy in chronic HCV genotype 4 patients

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