TY - JOUR T1 - Interleukin-1 Influences Ischemic Brain Damage in the Mouse Independently of the Interleukin-1 Type I Receptor JF - The Journal of Neuroscience JO - J. Neurosci. SP - 38 LP - 43 DO - 10.1523/JNEUROSCI.22-01-00038.2002 VL - 22 IS - 1 AU - Omar Touzani AU - Herve Boutin AU - Rosalind LeFeuvre AU - Lisa Parker AU - Andy Miller AU - Giamal Luheshi AU - Nancy Rothwell Y1 - 2002/01/01 UR - http://www.jneurosci.org/content/22/1/38.abstract N2 - The cytokine interleukin-1β (IL-1β) contributes to ischemic, excitotoxic, and traumatic brain injury. IL-1β actions depend on interaction with a single receptor (IL-1RI), which associates with an accessory protein (IL-1RAcP), and is blocked by IL-1 receptor antagonist (IL-1ra). Here we show that in normal mice [wild-type (WT)], intracerebroventricular injection of IL-1ra markedly reduces (−50%; p < 0.01) ischemic brain damage caused by reversible occlusion of the middle cerebral artery, whereas injection of IL-1β exacerbates damage (+45%; p < 0.05).Mice lacking IL-1RI [IL-1RI knock-out (KO)] exhibited ischemic brain damage that is almost identical to that of the WT (infarct volume 43.7 ± 6.1 and 46.2 ± 6.2 mm3, respectively), but failed to respond to injection of IL-1ra. However, injection of IL-1β (intracerebroventricularly) exacerbated ischemic brain damage in IL-1RI KO (+61%; p < 0.001) and in WT mice (+45%). This effect of IL-1β was abolished by heat denaturation in all animals, and was reversed by IL-1ra in WT, but not IL-1RI KO mice. In contrast, IL-1RI KO mice were completely resistant to effects of IL-1β on food intake or body weight. IL-1RAcP mRNA was increased by stroke in WT, but reduced in IL-1RI KO mice compared with sham-operated mice. Type II IL-1 receptor mRNA was significantly increased 4 hr after ischemia in WT and IL-1RI KO (+20%) animals.These data show that IL-1β can exacerbate ischemic brain damage independently of IL-1RI and suggest the existence of additional signaling receptor or receptors for IL-1 in the brain. ER -