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 r elation to expression of IL-1 alpha, IL-1 beta, and IL-6 mRNA was stud ied, 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. Animal s 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 m RNA for IL-1 alpha, IL-1 beta, and IL-6 with reverse transcription fol lowed by a polymerase chain reaction. In separate animals, IL-1ra was administered intracerebrally before or after HI, and the extent of bra in injury was assessed 14 d after HI. A transient increase of IL-1 bio activity occurred after HI, reaching a peak at 6 h of recovery. IL-1 b eta mRNA followed a similar time course but attained maximum expressio n at 3 h. IL-6 bioactivity and mRNA were also stimulated by HI and fol lowed 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 less than or eq ual to 0.01), and IL-1ra posttreatment increased the proportion of ani mals devoid of brain injury (40%) compared with vehicle-treated contro ls (13%) (p less than or equal to 0.05). In conclusion, a transient ac tivation of IL-1 and IL-6 occurred after HI, and IL-1ra reduced HI bra in injury to a moderate degree.