title: Why dapsone stops seizures and may stop neutrophils' delivery of VEGF to glioblastoma.
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.
authors.affiliation: Department of Psychiatry, University of Vermont, Burlington, VT 05401, USA. rekast@email.com
authors.forename: R E
authors.initials: RE
authors.lastname: Kast
authors.forename: F
authors.initials: F
authors.lastname: Lefranc
authors.forename: G
authors.initials: G
authors.lastname: Karpel-Massler
authors.forename: M-E
authors.initials: ME
authors.lastname: Halatsch
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000627:therapeutic use; D003622:Dapsone / Q000494:pharmacology* / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D012640:Seizures / Q000188:drug therapy*; D042442:Vascular Endothelial Growth Factors / Q000187:drug effects / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D042442:Vascular Endothelial Growth Factors; D003622:Dapsone