Critical Role of IL-8 Targeting in Gliomas

Kosmopoulos, Marinos; Christofides, Anthos; Drekolias, Dimitrios; Zavras, Phaedon D.; Gargalionis, Antonios N.; Piperi, Christina

doi:10.2174/0929867325666171129125712

Cited by 22 publications

(16 citation statements)

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“…Interestingly, VEGF-D, but not VEGF-C has effects in neuronal dendritic arborization and cognition [27]. We also described an increase in IL-8 for PD patients, a macrophage-secreted chemokine known to recruit neutrophils and monocytes and promote angiogenesis [39]. PD patients had also increased IL-15, a cytokine produced by multiple cell types including monocytes, neurons, and astrocytes [59].…”

Section: Discussionmentioning

confidence: 76%

“Changes in soluble CD163 indicate monocyte involvement in cognitive deficits in Parkinson’s disease”

Nissen

Ferreira

Schulte

et al. 2020

Preprint

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Parkinson's disease is a neurodegenerative disorder with a significant immune component. Numerous studies have reported alterations on immune biomarkers in CSF and serum that associate with symptoms in PD patients. However, it is unclear, which specific immune cells are responsible for the changes in those biomarkers; since most of these cytokines or chemokines, can be produced by a variety of immune cells, or even neurons or glia cells in the brain. Here, we investigate a monocyte/macrophage-specific biomarker: sCD163, the soluble form of the receptor CD163. Our data from tow cohorts show that the CSF-sCD163 increases as the disease progresses, together with a correlated increase in PD-specific as well as neurodegeneration-associated disease biomarkers: alpha-synuclein, tau, and phosphorylated-Tau. Moreover, CSF-sCD163 levels were inversely correlated to the cognitive scores MMSE and MOCA, with higher sCD163 indicating lower cognitive capacity. sCD163 was also increased in serum, although only in female PD patients, suggesting a gender distinctive monocyte-related immune response. CSF-sCD163 also correlated with molecules associated with endothelial cells, tissue infiltration, and activation of B cells and T cells in the PD patients. This suggests activation of both the adaptive and the innate immune system along with recruitment of lymphocytes and monocytes to sites of inflammation in the brain. In serum, sCD163 was associated with pro-inflammatory cytokines and acute phase proteins, suggesting a relation to chronic systemic inflammation. Interestingly, our in vitro study suggests that sCD163 might enhance alpha-synuclein uptake by myeloid cells without direct binding, thus participating in the clearance of alpha-synuclein. Accordingly, our data supports sCD163 as a potential cognition-related biomarker in PD and corroborates a role for monocytes both in peripheral and brain immune responses that could have direct consequences in the handling of alpha-synuclein

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Section: Discussionmentioning

confidence: 76%

“Changes in soluble CD163 indicate monocyte involvement in cognitive deficits in Parkinson’s disease”

Nissen

Ferreira

Schulte

et al. 2020

Preprint

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“…IL-8 is a cytokine of the chemokine family. IL-8 is mainly produced by endothelial cells, epithelial cells, fibroblasts, etc., and its active form is composed of 69, 72, 77, and 79 amino acids, respectively, and has a molecular weight of about 8 kDa [133]. The receptors for IL-8 are CXCR1 and CXCR2.…”

Section: Proinflammatory Factors and Inflammatory Factors In Chronic mentioning

confidence: 99%

Chronic inflammation: key player and biomarker-set to predict and prevent cancer development and progression based on individualized patient profiles

2019

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A strong relationship exists between tumor and inflammation, which is the hot point in cancer research. Inflammation can promote the occurrence and development of cancer by promoting blood vessel growth, cancer cell proliferation, and tumor invasiveness, negatively regulating immune response, and changing the efficacy of certain anti-tumor drugs. It has been demonstrated that there are a large number of inflammatory factors and inflammatory cells in the tumor microenvironment, and tumor-promoting immunity and anti-tumor immunity exist simultaneously in the tumor microenvironment. The typical relationship between chronic inflammation and tumor has been presented by the relationships between Helicobacter pylori, chronic gastritis, and gastric cancer; between smoking, development of chronic pneumonia, and lung cancer; and between hepatitis virus (mainly hepatitis virus B and C), development of chronic hepatitis, and liver cancer. The prevention of chronic inflammation is a factor that can prevent cancer, so it effectively inhibits or blocks the occurrence, development, and progression of the chronic inflammation process playing important roles in the prevention of cancer. Monitoring of the causes and inflammatory factors in chronic inflammation processes is a useful way to predict cancer and assess the efficiency of cancer prevention. Chronic inflammation-based biomarkers are useful tools to predict and prevent cancer.

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“…IL-8 is integral to GB tumor cell proliferation, invasion, and vascular mimicry [11]. Details follow: IL-8 is an 11 kDa cytokine that comprises an integral, core feature of GB's pathophysiology [12]. In addition to the data collected and analyzed in our previous GB-related dapsone papers referenced above, recent reports confirm IL-8 as contributing to GB cells' migration, vascular mimicry, and proliferation, as well as the established role of IL-8 as a central chemotaxic signal for neutrophil homing [11][12][13][14][15].…”

Section: Gb and Il-8mentioning

confidence: 99%

Research Supporting a Pilot Study of Metronomic Dapsone during Glioblastoma Chemoirradiation

Kast¹

2021

Medical Sciences

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This short note presents previous research data supporting a pilot study of metronomic dapsone during the entire course of glioblastoma treatment. The reviewed data indicate that neutrophils are an integral part of human glioblastoma pathophysiology, contributing to or facilitating glioblastoma growth and treatment resistance. Neutrophils collect within glioblastoma by chemotaxis along several chemokine/cytokine gradients, prominently among which is interleukin-8. Old data from dermatology research has shown that the old and inexpensive generic drug dapsone inhibits neutrophils’ chemotaxis along interleukin-8 gradients. It is on that basis that dapsone is used to treat neutrophilic dermatoses, for example, dermatitis herpetiformis, bullous pemphigoid, erlotinib-related rash, and others. The hypothesis of this paper is that dapsone will reduce glioblastomas’ neutrophil accumulations by the same mechanisms by which it reduces dermal neutrophil accumulations in the neutrophilic dermatoses. Dapsone would thereby reduce neutrophils’ contributions to glioblastoma growth. Dapsone is not an ideal drug, however. It generates methemoglobinemia that occasionally is symptomatic. This generation is reduced by concomitant use of the antacid drug cimetidine. Given the uniform lethality of glioblastoma as of 2020, the risks of dapsone 100 mg twice daily and cimetidine 400 mg twice daily is low enough to warrant a judicious pilot study.

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Critical Role of IL-8 Targeting in Gliomas

Abstract: Several promising approaches that target directly or indirectly IL-8 effects in gliomas are currently in progress while more-in-depth studies are needed to validate its biomarker role and elucidate the underlying molecular mechanisms.

Cited by 22 publications

References 0 publications

“Changes in soluble CD163 indicate monocyte involvement in cognitive deficits in Parkinson’s disease”

“Changes in soluble CD163 indicate monocyte involvement in cognitive deficits in Parkinson’s disease”

Chronic inflammation: key player and biomarker-set to predict and prevent cancer development and progression based on individualized patient profiles

Research Supporting a Pilot Study of Metronomic Dapsone during Glioblastoma Chemoirradiation

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