Enhanced expression of interleukin (IL)-1 and IL-6 messenger RNA and bioactive protein after hypoxia-ischemia in neonatal rats.
The effect of hypoxia-ischemia (HI) on IL-1, and IL-6 bioactivity in relation to expression of IL-1 alpha, IL-1 beta, and IL-6 mRNA was studied, and the neuroprotective efficacy of IL-1 receptor antagonist (IL-1ra) was evaluated in neonatal rats. HI was induced in 7-d-old rats by unilateral carotid artery ligation and hypoxia for 70-100 min. Animals were killed at different time points up to 14 d after HI, and brains were analyzed for IL-1 and IL-6 bioactivity using bioassays and for mRNA for IL-1 alpha, IL-1 beta, and IL-6 with reverse transcription followed by a polymerase chain reaction. In separate animals, IL-1ra was administered intracerebrally before or after HI, and the extent of brain injury was assessed 14 d after HI. A transient increase of IL-1 bioactivity occurred after HI, reaching a peak at 6 h of recovery. IL-1 beta mRNA followed a similar time course but attained maximum expression at 3 h. IL-6 bioactivity and mRNA were also stimulated by HI and followed a similar time course as IL-1. Pretreatment with IL-1ra reduced HI brain damage from 54.4 +/- 9.3 to 41.4 +/- 10.0% (p < or = 0.01), and IL-1ra posttreatment increased the proportion of animals devoid of brain injury (40%) compared with vehicle-treated controls (13%) (p < or = 0.05). In conclusion, a transient activation of IL-1 and IL-6 occurred after HI, and IL-1ra reduced HI brain injury to a moderate degree.
Department of Obstetrics and Gynecology, University of Göteborg, Sweden.
H
H
Hagberg
E
E
Gilland
E
E
Bona
L A
LA
Hanson
M
M
Hahin-Zoric
M
M
Blennow
M
M
Holst
A
A
McRae
O
O
Söder
D000818:Animals; D000831:Animals, Newborn; D001681:Biological Assay; D001786:Blood Glucose / Q000378:metabolism; D001831:Body Temperature; D001921:Brain / Q000276:immunology*; D001930:Brain Injuries / Q000276:immunology; D017931:DNA Primers; D006801:Humans; D002534:Hypoxia, Brain / Q000276:immunology*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D002546:Ischemic Attack, Transient / Q000276:immunology*; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D001786:Blood Glucose; D017931:DNA Primers; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012795:Sialoglycoproteins