IL-1β induction and IL-6 suppression are associated with aggravated neuronal damage in a lipopolysaccharide-pretreated kainic acid-induced rat pup seizure model.
OBJECTIVE
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.


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.
Department of Neurology, College of Medicine, Chungbuk National University Cheongju, Chungbuk, Republic of Korea.
Sung-Hyun
SH
Lee
Bong-Je
BJ
Kim
Yong Bum
YB
Kim
Pil-Wook
PW
Chung
Heui-Soo
HS
Moon
Bum Chun
BC
Suh
Won Tae
WT
Yoon
Dong-Kwan
DK
Jin
Yong Shik
YS
Park
Yong-Taek
YT
Lee
Kwang-Yeol
KY
Park
D000818:Animals; D000831:Animals, Newborn; D001831:Body Temperature / Q000187:drug effects; D001930:Brain Injuries / Q000209:etiology* / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy; D018709:Statistics, Nonparametric; D013226:Status Epilepticus / Q000139:chemically induced / Q000150:complications; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D018690:Excitatory Amino Acid Agonists; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D007608:Kainic Acid