Why dapsone stops seizures and may stop neutrophils’ delivery of VEGF to glioblastoma
- 2 May 2012
- journal article
- review article
- Published by Taylor & Francis Ltd in British Journal of Neurosurgery
- Vol. 26 (6), 813-817
- https://doi.org/10.3109/02688697.2012.674577
Abstract
Lopez-Gomez et al. recently published remarkable but mechanistically unexplained empirical evidence that the old antibiotic dapsone has antiepileptic activity. We addressed the question “Why should a sulfone antibiotic reduce seizures?”. We report here our conclusions based on data from past studies that seizures are associated with elevated interleukin-8 (IL-8) and that dapsone inhibits IL-8 release and function in several different clinical and experimental contexts. Diverse CNS insults cause an increase in CNS IL-8. Thus, the pro-inflammatory environment generated by increase IL-8 leads to a lower seizure threshold. Together this evidence indicates dapsone exerts anti-seizure activity by diminishing IL-8 signalling. Since IL-8 is clearly upregulated in glioblastoma and contributes to the florid angiogenesis of that disease, and since interference with IL-8 function has been shown to inhibit glioblastoma invasion and growth in several experimental models, and dapsone has been repeatedly been shown to clinically inhibit IL-8 function when used to treat human neutrophilic dermatoses, we believe that dapsone thereby reduces seizures by countering IL-8 function and may similarly retard glioblastoma growth by such anti-IL-8 function.Keywords
This publication has 56 references indexed in Scilit:
- Glia maturation factor-γ mediates neutrophil chemotaxisJournal of Leukocyte Biology, 2011
- CXC chemokine receptor 1 enhances the ability of human umbilical cord blood-derived mesenchymal stem cells to migrate toward gliomasBiochemical and Biophysical Research Communications, 2011
- Hepatitis C Virus Core Protein Induces Neuroimmune Activation and Potentiates Human Immunodeficiency Virus-1 NeurotoxicityPLOS ONE, 2010
- Levetiracetam enhances p53-mediated MGMT inhibition and sensitizes glioblastoma cells to temozolomideNeuro-Oncology, 2010
- Knockdown of CypA inhibits interleukin-8 (IL-8) and IL-8-mediated proliferation and tumor growth of glioblastoma cells through down-regulated NF-κBJournal of Neuro-Oncology, 2010
- Cytokines and chemokines in viral encephalitis: A clinicoradiological correlationNeuroscience Letters, 2010
- Cellular injury and neuroinflammation in children with chronic intractable epilepsyJournal of Neuroinflammation, 2009
- Correlation of enzyme-inducing anticonvulsant use with outcome of patients with glioblastomaNeurology, 2009
- Analysis of interleukin (IL)-8 expression in human astrocytomas: Associations with IL-6, cyclooxygenase-2, vascular endothelial growth factor, and microvessel morphometryHuman Immunology, 2009
- Deregulation of a STAT3-Interleukin 8 Signaling Pathway Promotes Human Glioblastoma Cell Proliferation and InvasivenessJournal of Neuroscience, 2008