Tumor Necrosis Factor‐α and Interleukin‐6 Concentrations in Cerebrospinal Fluid of Dogs After Seizures

Abstract

BackgroundIdiopathic and acquired epilepsy are common in dogs. Up to 30% of these dogs are refractory to pharmacological treatment. Accumulating experimental evidence indicates that brain immune response and presence of inflammatory mediators decrease the threshold for individual seizures and contribute to epileptogenesis.HypothesisDogs with seizures have higher cerebrospinal interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) concentrations compared to dogs with no seizures.MethodsA prospective double blinded study; cerebrospinal fluid (CSF) and serum IL‐6, TNF‐α and total protein (TP) concentrations were measured by a blinded investigator for the study group and CSF IL‐6 and TNF‐α levels and TP concentrations were measured in the control group (CG).AnimalsDogs presented with seizures that had enough CSF collected to allow analysis were included in the study group. Twelve apparently healthy, quarantined, stray dogs served as control (CG).ResultsCerebrospinal fluid TNF‐α and IL‐6 concentrations were significantly higher (P = .011, P = .039) in dogs with seizures (0 ± 70.66, 0.65 ± 10.93 pg/mL) compared to the CG (0 ± 19, 0.73 ± 0.55 pg/mL). When assessing cytokine concentrations of specifically the idiopathic epilepsy (IE) dogs compared to the CG, only TNF‐α concentrations (8.66 ± 62, 0 ± 19 pg/mL) were significantly higher (P = .01). CSF TP concentrations were not significantly higher in the study dogs compared to the CG.Conclusions and Clinical ImportanceHigher TNF‐α and IL‐6 concentration in the CSF of dogs with naturally occurring seizures. The higher supports the hypothesis that inflammatory processes through certain mediators play a role in the pathogenesis of seizures in dogs.

The Role of NLRP3 and IL-1β in Refractory Epilepsy Brain Injury

“…patients with different seizure types reflected the severity of epilepsy (16)(17)(18). Dubé et al found that inflammatory cytokines (such as IL-1β) played a crucial role in epilepsy caused by febrile seizures in children (19).…”

Neuroinflammation in Epilepsy—Diagnostics and Therapeutic Perspectives

“…Increased IL-1β was detected in the peripheral blood in dogs with epilepsy regardless of the cause [32]. In the CSF of dogs with naturally occurring seizures, significantly higher TNF-α and IL-6 concentrations were found [33]. In the forebrain of rats, IL-6 and TNF-α levels were increased after acute seizure, but only briefly, in contrast to IL-1β, which did not return to baseline levels even after the seizure had subsided [34].…”

Astrocytes as Guardians of Neuronal Excitability: Mechanisms Underlying Epileptogenesis

“…Numerous studies have shown upregulation of IL-1β, IL-6, and TNF-α in animals with (recurrent) seizures (53)(54)(55)(56)(57)(58)(59) and patients with epilepsy (60)(61)(62)(63). IL-1β can affect neurotransmitter receptors (64,65), induce calcium influx by N-methyl-D-aspartate (NMDA) and 3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-mediated mechanisms in neurons (66,67), lead to alterations in expression of microRNAs in astrocytes (68)(69)(70), as well as potassium channels (71), metalloproteinases (72), altered astrocytic glutamate uptake (73,74) and calcium uptake (75), and induces astrocytic release of other pro-inflammatory cytokines (50).…”