Expression of interleukin-16 by tumor-associated macrophages/activated microglia in high-grade astrocytic brain tumors

Liebrich, M.; Guo, Liang-Hao; Schluesener, Hermann J.; Schwab, Jan M.; Dietz, Klaus; Will, B.; Meyermann, Richard

doi:10.1007/s00005-007-0003-0

Cited by 42 publications

(36 citation statements)

References 24 publications

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“…In the relapsing form of multiple sclerosis, IL-16 has come under close scrutiny for its possible role in neuroinflammation and axonal damage [14] . Similar findings have been described when investigating the role of IL-16 in cerebral infarctions and astrocytic brain tumours [15,16] . Along with its function in inflammatory cell activation and the induction of proinflammatory cytokine release, IL-16 has also been associated with induction of increased intracellular calcium or inositol-(1, 4, 5)-triphosphate and the translocation of protein kinase C, all of which can lead to neuronal ischaemic cell death [7] .…”

Section: Discussionsupporting

confidence: 70%

“…Prior to this work, levels of IL-16 in neonatal hypoxia-ischaemia had not been described. However, IL-16 alterations have been identified in other pathologies of the nervous system, specifically multiple sclerosis, autoimmune encephalomyelitis, cerebral infarctions, spinal cord injuries and astrocytic brain tumours [7,[14][15][16] . The role of IL-16 remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Cord Blood IL-16 Is Associated with 3-Year Neurodevelopmental Outcomes in Perinatal Asphyxia and Hypoxic-Ischaemic Encephalopathy

Ahearne¹,

Chang

Walsh

et al. 2017

Dev Neurosci

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Activation of the inflammatory pathway is increasingly recognized as an important mechanism of injury following neonatal asphyxia and encephalopathy. This process may contribute to the poor prognosis seen in some cases, despite therapeutic hypothermia. Our group has previously identified raised interleukin (IL)-6 and IL-16, measured in umbilical cord blood at birth, to be predictive of grade of hypoxic-ischaemic encephalopathy (HIE). Our aim in this study was to examine the ability of these cytokines to predict the 3-year neurodevelopmental outcome in the same cohort. As part of a prospective, longitudinal cohort study set in a single tertiary maternity unit, term infants with biochemical and clinical evidence of perinatal asphyxia were recruited at birth. Umbilical cord blood was collected and analyzed for IL-6 and IL-16 using a Luminex assay. The neurodevelopmental outcome of these infants was assessed at 3 years using the Bayley Scales of Infant and Toddler Development (Edition 3). Early cord blood measurement of IL-6 and IL-16 and long-term outcome were available in 33/69 infants. Median (IQR) IL-16 differentiated infants with a severely abnormal outcome (n = 6) compared to all others (n = 27), (646 [466-1,085] vs. 383.5 [284-494] pg/mL; p = 0.012). IL-16 levels were able to predict a severe outcome with an area under the receiver-operating characteristic (ROC) curve of 0.827 (95% CI 0.628-1.000; p = 0.014). Levels ≥514 pg/mL predicted a severe outcome with a sensitivity of 83% and a specificity of 81%. IL-16 also outperformed other routine biochemical markers available at birth for the prediction of severe outcome. APGAR scores at 1 and 10 min were also predictive of a severe outcome (p = 0.022 and p = 0.036, respectively). A combination of IL-16 with these clinical markers did not improve predictive value, but IL-16 combined with electroencephalogram grading increased the area under the ROC curve. IL-6 did not show any association with 3-year outcome. This is the first report studying the association of IL-16 measured at birth with long-term outcome in a cohort of neonates with perinatal asphyxia. IL-16 may be an early biomarker of severe injury and aid in the long-term prognostication in infants with HIE.

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Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Cord Blood IL-16 Is Associated with 3-Year Neurodevelopmental Outcomes in Perinatal Asphyxia and Hypoxic-Ischaemic Encephalopathy

Ahearne¹,

Chang

Walsh

et al. 2017

Dev Neurosci

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“…The expression of IL16 in prostatectomy tumor specimens from Pca patients is positively correlated with Gleason score and pathological stage (54), and high expression of IL16 has been observed in other types of tumor cells (55, 56). The serum levels of IL-16 protein are also elevated in patients with other types of cancers, especially patients in advanced stages of cancer (57, 58).…”

Section: Discussionmentioning

confidence: 99%

Fine-Mapping of IL16 Gene and Prostate Cancer Risk in African Americans

Batai

Shah

Newsome

et al. 2012

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Prostate cancer (Pca) is the most common type of cancer among men in the United States, and its incidence and mortality rates are disproportionate among ethnic groups. While genome-wide association studies of European descents have identified candidate loci associated with Pca risk, including a variant in IL16, replication studies in African Americans (AAs) have been inconsistent. Here we explore SNP variation in IL16 in AAs and test for association with Pca. Methods Association tests were performed for 2,257 genotyped and imputed SNPs spanning IL16 in 605 AA Pca cases and controls from Washington, DC. Eleven of them were also genotyped in a replication population of 1,093 AAs from Chicago. We tested for allelic association adjusting for age, global and local West African ancestry. Results Analyses of genotyped and imputed SNPs revealed that a cluster of IL16 SNPs were significantly associated with Pca risk. The strongest association was found at rs7175701 (P=9.8 × 10−8). In the Chicago population, another SNP (rs11556218) was associated with Pca risk (P=0.01). In the pooled analysis, we identified three independent loci within IL16 that were associated with Pca risk. SNP eQTL analyses revealed that rs7175701 is predicted to influence the expression of IL16 and other cancer related genes. Conclusion Our study provides evidence that IL16 polymorphisms play a role in Pca susceptibility among AAs. Impact Our findings are significant given that there has been limited focus on the role of IL16 genetic polymorphisms on Pca risk in AAs.

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“…The correlation between circulating IL-16 and growth hormone with glioma patient survival were not well-known. At the tissue level, the percentage of IL-16 positive cells has been shown to be increased significantly in studies comparing control human brains and WHO grade II brain tumors to anaplastic astrocytoma and GBM (36). GH, a pituitary hormone, has been shown to enhance natural killer cell activity against glioma (37).…”

Section: Discussionmentioning

confidence: 99%

Identification of blood protein biomarkers that aid in the clinical assessment of patients with malignant glioma

Gowda

et al. 2012

Int J Oncol

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Abstract. Analyzing molecular biomarkers using blood is an important approach for clinical assessment of malignant glioma. We investigated a molecular proteomic biomarkerbased approach for glioblastoma using patients' blood samples. The expression levels of a list of candidate proteins were quantified in plasma and serum samples from two different cohorts of patients with malignant glioma and normal controls. The biological function was studied for one of the identified markers. Additionally, the prognostic significance of protein marker expression was measured by survival analysis. As a result, protein biomarkers associated with malignant glioma were identified from the blood specimens and five of the protein biomarkers were common to both cohorts. Immunohistochemical analysis demonstrated that many of the protein biomarkers identified in peripheral blood specimens were expressed in malignant gliomas. Staining levels for one of the biomarkers, MIP-1α, was found to correlate with WHO grade among invasive gliomas, and we demonstrate that MIP-1α promotes human glioblastoma cell proliferation and migration. Additionally, four prognostic protein biomarkers were identified. In conclusion, we demonstrate that both peripheral blood plasma and serum specimens are highly valuable and complementary to each other in the quest for protein biomarkers of malignant glioma. Sets of novel protein biomarkers were identified that may aid in the diagnosis and prognosis of patients with malignant glioma.

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Expression of interleukin-16 by tumor-associated macrophages/activated microglia in high-grade astrocytic brain tumors

Cited by 42 publications

References 24 publications

Cord Blood IL-16 Is Associated with 3-Year Neurodevelopmental Outcomes in Perinatal Asphyxia and Hypoxic-Ischaemic Encephalopathy

Cord Blood IL-16 Is Associated with 3-Year Neurodevelopmental Outcomes in Perinatal Asphyxia and Hypoxic-Ischaemic Encephalopathy

Fine-Mapping of IL16 Gene and Prostate Cancer Risk in African Americans

Identification of blood protein biomarkers that aid in the clinical assessment of patients with malignant glioma

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