Enhanced expression of interleukin (IL)-1 and IL-6 messenger RNA and bioactive protein after hypoxia-ischemia in neonatal rats

Pediatr Res. 1996 Oct;40(4):603-9. doi: 10.1203/00006450-199610000-00015.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biological Assay
  • Blood Glucose / metabolism
  • Body Temperature
  • Brain / immunology*
  • Brain Injuries / immunology
  • DNA Primers
  • Humans
  • Hypoxia, Brain / immunology*
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / biosynthesis*
  • Interleukin-6 / biosynthesis*
  • Ischemic Attack, Transient / immunology*
  • Polymerase Chain Reaction / methods
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Wistar
  • Recombinant Proteins / pharmacology
  • Sialoglycoproteins / pharmacology*
  • Transcription, Genetic* / drug effects


  • Blood Glucose
  • DNA Primers
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Interleukin-6
  • RNA, Messenger
  • Recombinant Proteins
  • Sialoglycoproteins