IL-1β Induction and IL-6 Suppression Are Associated with Aggravated Neuronal Damage in a Lipopolysaccharide-Pretreated Kainic Acid-Induced Rat Pup Seizure Model

Abstract

Objectives: Reportedly, hippocampal neuronal degeneration by kainic acid (KA)-induced seizures in rats <14 days old was enhanced by lipopolysaccharide (LPS). This study was to test the hypothesis that cytokines such as interleukin (IL)-1β, IL-6 and tumor necrosis factor-α are associated with aggravated neuronal damage. Materials and Methods: Sixty male Sprague-Dawley, 14-day-old rats were used. Experiments were conducted in saline, LPS + saline, saline + KA and LPS + KA groups. Intraperitoneal LPS injections (0.04 mg/kg) were administered 3 h prior to KA injection (3 mg/kg). Results: The LPS + KA group showed a tendency toward shorter latency to seizure onset (p = 0.086) and significantly longer seizure duration (p < 0.05) compared with the KA group. Induction of the proconvulsant cytokine IL-1β in rat pup brains was significantly greater in the LPS + KA group compared to the KA group (38.8 ± 5.5 vs. 9.2 ± 1.0 pg/µg; p < 0.05); however, IL-6 levels were higher in the KA group than in the LPS + KA group (108.7 ± 6.8 vs. 60.9 ± 4.7 pg/µg; p < 0.05). The difference in tumor necrosis factor-α between the LPS + KA group and the KA group was insignificant (12.1 ± 0.6 vs. 10.9 ± 2.3 pg/µg; p = 0.64). Conclusions: Our results showed an increase in the proconvulsant cytokine IL-1β and a decrease in a potentially neuroprotective cytokine, IL-6, in rat pups treated with LPS + KA. These results warrant further investigation into the possible role of IL-1β induction and IL-6 suppression in LPS-promoted neuronal damage.

Role of the Toll-like receptor 3 signaling pathway in the neuroprotective effect of sevoflurane pre-conditioning during cardiopulmonary bypass in rats

“…The serum concentration of IL-6 was in parallel with the size of the cerebral infarction area, an independent risk factor of brain damage. The possible mechanisms is the promotion of aggregation and adhesion of inflammatory cells, partial infarction of brain tissue, activation of matrix metalloproteinases, destruction of the blood-brain barrier, stimulation of platelet activity, promotion of fibrinogen production and reduction of cerebral perfusion ( 42 – 45 ).…”

Pre- and Neonatal Exposure to Lead (Pb) Induces Neuroinflammation in the Forebrain Cortex, Hippocampus and Cerebellum of Rat Pups

“…It has been shown that IL-1β is important in the neurotoxicity of LPS [71,72] and secondary brain injury caused by neuroinflammation during traumatic brain injury [73] and ischemia [74][75][76]. Although IL-1β and neuroinflammation may act protectively in certain brain injuries [77], for example improving the function of the blood-brain barrier after injury [78,79].…”

“…Due to the varied action of IL-6, its Pb-induced increase in different parts of the brain can have both positive and negative consequences. IL-6 has been shown to exert both a cytoprotective [71,85,86] and destructive pro-inflammatory [87,88] effect in various studies of neuroinflammation induced by LPS. It is likely that in our research model IL-6 regulates excessive neuroinflammation and protects against extensive damage to brain tissue, which requires clarification through further research on the effects of IL-6 on the brain of animals treated with Pb.…”

Expression of Cytokines and Neurodegeneration in the Rat Hippocampus and Cortex in the Lithium-Pilocarpine Model of Status Epilepticus and the Role of Modulation of Endocannabinoid System

“…Inhibition of CB1 receptors early after SE suppressed the increase in the expression of Il6 in the hippocampus in the chronic period. There are reports that IL-6, while promoting inflammatory response, can have a neuroprotective effect via the JAK/STAT3 and RAS/MAPK pathways [ 35 , 36 , 37 ], and suppression of Il6 expression could aggravate neurodegeneration [ 37 ]. Other studies showed that in epilepsy models, Il6 upregulation could aggravate neuronal damage [ 38 ].…”