One edemogenic factor involved in brain edema formation after ICH is thrombin.19–22,40 Therefore, inhibiting the inflammatory reaction might reduce thrombin-induced brain edema after ICH, because thrombin triggers an inflammatory response in many tissues,5 including brain.31
Interleukin-1 is a potent inflammatory mediator. Levels of IL-1 in the brain increase after ischemia, injection of bacterial endotoxin, and local brain injury.35,46 The IL-1ra inhibits several actions of IL-1, both in vivo and in vitro,7 and administration of IL-1ra reduces ischemic and traumatic brain injury.23–25,33,37 Gene transfer has proven to be a useful tool to study the mechanisms of action of IL-1 in vivo, as shown by studies of adenovirus-mediated overexpression of IL-1ra, which attenuates ischemic brain injury.3,46 The effect of IL-1ra on ICH has not been studied, and because ischemia does not appear to be a significant contributor to brain injury following ICH (see, for example, Patel, et al.32) the effects of this antagonist on ICH are uncertain.
In this study we examine whether adenovirus-mediated overexpression of IL-1ra can reduce the brain edema that follows ICH or thrombin instillation into the basal ganglia, and whether IL-1ra overexpression reduces the thrombininduced inflammatory response. We used MPO activity as a marker of PMNLs to assess the thrombin-induced inflammatory reaction.1
Dvorak HF: Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315:1650–16591986Dvorak HF: Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315:
Kaplanski GMarin VFabrigoule Met al: Thrombin-activated human endothelial cells support monocyte adhesion in vitro following expression of intercellular adhesion molecule-1 (ICAM-1; CD54) and vascular cell adhesion molecule-1 (VCAM-1; CD106). Blood 92:1259–12671998Blood 92:
This study was supported by National Institutes of Health Grant No. NS-17760 to Dr. Hoff, NS-35089 to Dr. Yang, and NS-39866 to Dr. Xi.