Overexpression of interleukin-1 receptor antagonist reduces brain edema induced by intracerebral hemorrhage and thrombin.

Recent studies indicate that inflammatory reaction occurs around hematoma after intracerebral hemorrhage (ICH). In this study the authors examine the hypothesis that overexpression of IL-1ra in the brain attenuate brain edema formation after ICH. Adenoviruses expressing IL-1ra (Ad.RSVIL-1ra) or LacZ (Ad.RSVLacZ) or saline were injected into the lateral ventricle. On the fifth day after virus injection, 100 microl of autologous blood or 5 U thrombin was infused into the right basal ganglia. Rats with ICH were killed 24 or 72 hours later for measurement of brain water content. Thrombin-treated rats were killed 24 hours later for edema measurements and an assessment of polymorphonuclear leukocyte (PMNL) infiltration by myeloperoxidase (MPO) assay. Compared with control groups, Ad.RSVIL-1ra treated rats had less brain edema formation in the ipsilateral basal ganglia 3 days after ICH (81.5 +/- 0.3% compared with 83.4 +/- 0.4% and 83.3 +/- 0.5% in control animals). Ad.RSVIL-1ra treated rats had also less brain edema following thrombin injection. The reduction of brain edema induced by thrombin was involved in the reduction of PMNL infiltration in basal ganglia, as assessed by MPO assay. Adenovirus-mediated overexpression of IL-1ra attenuated brain edema formation following ICH, perhaps by reduction of thrombin-induced brain inflammation.