Why dapsone stops seizures and may stop neutrophils' delivery of VEGF to glioblastoma

Br J Neurosurg. 2012 Dec;26(6):813-7. doi: 10.3109/02688697.2012.674577. Epub 2012 May 2.

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.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Anti-Infective Agents / therapeutic use
  • Dapsone / pharmacology*
  • Dapsone / therapeutic use*
  • Drug Delivery Systems / methods*
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology*
  • Humans
  • Neutrophils / drug effects*
  • Neutrophils / metabolism*
  • Seizures / drug therapy*
  • Vascular Endothelial Growth Factors / drug effects
  • Vascular Endothelial Growth Factors / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Vascular Endothelial Growth Factors
  • Dapsone