title: Inflammation and iron metabolism in adult patients with epilepsy: does a link exist?
abstract: OBJECTIVE
  Inflammation has been shown to play a key role in epilepsy, and may also affect both the iron status and metabolism. Consequently, a relationship between iron metabolism and neuronal excitability and seizures could be expected.
  
  
  METHODS
  We aimed at characterizing in 37 adult patients affected by focal epilepsy during the interictal period serum inflammatory cytokines, such as interleukin 6 (IL-6), IL-6 soluble receptor (IL6-sR), interleukin 1 (IL-1), IL-1 receptor-antagonist (IL-1RA), tumor necrosis factor-α (TNF-α), and markers of iron status and metabolism: hemoglobin concentration (Hgb), mean corpuscular volume (MCV), hematocrit (Hct) red blood cell (RBC) count, serum iron and copper concentrations, ceruloplasmin (iCp), the ceruloplasmin enzymatic activity (eCp), the specific ceruloplasmin activity (eCp/iCp), total ferroxidase activity, transferrin (Tf), serum ferritin (SF), Tf saturation (Sat-Tf), and ratio of ceruloplasmin to transferrin (Cp/Tf). We investigated the correlations between these biological markers as well their relationship with patients' clinical features. A group of 43 healthy subjects had the same serologic measurements to serve as controls.
  
  
  RESULTS
  Our findings showed in the group of patients with epilepsy an increase of IL-6 (p=0.026) and a decrease of TNF-α (p=0.002) with respect to healthy subjects. For the first time, we also detected significant changes in iron metabolism as an increase of Cp/Tf (p=0.011) and a decrease of Tf (p=0.031), possibly driven by cytokine modifications and consistent with inflammation as acute phase and antioxidant activity markers. Accordingly, TNF-α positively correlated with Tf (p=0.005). Finally, a significant positive correlation between seizures frequency and eCp (p=0.046) and inversely with Hgb (p=0.038) and Hct (p=0.041), and an inverse correlation between TNF-α and the duration of epilepsy (p=0.021) was detected.
  
  
  CONCLUSIONS
  Our findings demonstrate a relevant relationship between epilepsy and systemic inflammation, with a consistent link between seizures, inflammatory cytokines (IL-6 and TNF-α) and iron regulation and metabolism, as acute phase and antioxidant markers.
authors.affiliation: Neurology, Campus Bio-Medico University, Rome, Italy. Electronic address: m.tombini@unicampus.it.
authors.forename: M
authors.initials: M
authors.lastname: Tombini
authors.forename: R
authors.initials: R
authors.lastname: Squitti
authors.forename: F
authors.initials: F
authors.lastname: Cacciapaglia
authors.forename: M
authors.initials: M
authors.lastname: Ventriglia
authors.forename: G
authors.initials: G
authors.lastname: Assenza
authors.forename: A
authors.initials: A
authors.lastname: Benvenga
authors.forename: G
authors.initials: G
authors.lastname: Pellegrino
authors.forename: C
authors.initials: C
authors.lastname: Campana
authors.forename: F
authors.initials: F
authors.lastname: Assenza
authors.forename: M
authors.initials: M
authors.lastname: Siotto
authors.forename: L
authors.initials: L
authors.lastname: Pacifici
authors.forename: A
authors.initials: A
authors.lastname: Afeltra
authors.forename: P M
authors.initials: PM
authors.lastname: Rossini
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D004827:Epilepsy / Q000097:blood* / Q000175:diagnosis; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D007501:Iron / Q000097:blood*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007501:Iron
keywords: Cytokines; Epilepsy; IL-6; Inflammation; Iron; TNF-α