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

초록

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)-1 beta, IL-6 and tumor necrosis factor-alpha 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-1 beta 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/mu g; 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/mu g; p < 0.05). The difference in tumor necrosis factor-alpha between the LPS + KA group and the KA group was insignificant (12.1 +/- 0.6 vs. 10.9 +/- 2.3 pg/mu g; p = 0.64). Conclusions: Our results showed an increase in the proconvulsant cytokine IL-beta 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-1 beta induction and IL-6 suppression in LPS-promoted neuronal damage. Copyright (C) 2012 S. Karger AG, Basel

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