Interleukin-1β and adverse effects on cerebral blood flow during long-term global hypoperfusion

Object. The effects of interleukin (IL)-1beta on the cerebral vasculature are complex and incompletely understood. Many pathophysiological states in which inflammatory cascades have been implicated also have varying degrees of cerebral hypoperfusion. The purpose of this investigation was to examine the long-term effects of this proinflammatory cytokine and its antagonist on cerebral blood flow (CBF) following global cerebral hypoperfusion. Methods. Sprague-Dawley rats were randomly assigned to 12 groups and given continuous intracerebroventricular (ICV) infusions of IL-1beta, the IL-1 receptor antagonist (IL-1ra), or saline vehicle (control). Global cerebral hypoperfusion was produced by occlusion of both carotid arteries and one vertebral artery. Cerebral blood flow was measured at baseline and again after initiation of the infusions by performing a Xe-133 clearance study. Prolonged ICV administration of IL-1beta resulted in a significant decrease in CBF compared with that in controls. Prolonged administration of the antagonist IL-1ra resulted in significant increases in CBF compared with that in both IL-1beta-treated animals and controls. Conclusions. This experiment demonstrates that long-term treatment with the proinflammatory cytokine IL-1beta adversely affects CBF.