Table 1B. Studies on the neuroprotective or neurotoxic effect of IL-1β in experimental stroke.
| Ischemia model | Strain | Intervention | Results | Effect of IL-1β | Reference |
|---|---|---|---|---|---|
| Mouse | |||||
| Distal pMCAO (electrocoagulation) | BALB/c | s.c. injection of 100 mg/kg IL-1Ra, immediately and 4 hours after surgery | IL-1Ra decreased infarct volume | Neurotoxic | Nawashiro et al (1997b) |
| Proximal tMCAO (30 minutes, filament) | IL-1β-KO IL-1α-KO IL-1αβ-KO C57BL/6 | i.c.v. injection of rhIL-1Ra 30 minutes before surgery and 40 minutes after tMCAO | IL-1αβ-KO mice displayed smaller infarct volumes than C57BL/6 No change in IL-1β-KO or IL-1α-KO rhIL-1Ra reduced infarct volume in C57BL/6 and IL-1α-KO mice but not in IL-1β-KO or IL-1αβ-KO mice | Neurotoxic | Boutin et al (2001) |
| Proximal tMCAO (2 hours, filament) | SV-129 | i.c.v. injection of ICE-like protease inhibitors (2 × 40 or 2 × 120 ng z-VAD.FMK, 2 × 200 ng YVAD.CMK, 2 × 120 ng z-DEVD.FMK) 15 minutes before surgery and again immediately after reperfusion or 45 minutes before surgery and again immediately after reperfusion | ICE-like protease inhibitors reduced infarct volumes | Neurotoxic | Hara et al (1997b) |
| Proximal tMCAO (3 hours, filament) | ICE-KO | — | ICE-KO mice displayed smaller infarct volumes than control mice | Neurotoxic | Hara et al (1997a) |
| Proximal tMCAO (30 minutes, filament) | IL-1RI-KO C57xSV129 | i.c.v. injection of 2 × 2.5 μg rhIL-1Ra and 2 × 2.5 ng IL-1β, respectively, 10 minutes before and 40 minutes after occlusion | rhIL-1Ra reduced infarct volume in C57xSV129 mice and IL-1β increased infarct volume in IL-1RI-KO and C57xSV129 mice | Neurotoxic | Touzani et al (2002) |
| Proximal tMCAO (1 hour, filament) | IL-1αβ-KO WT LM | — | IL-1αβ-KO mice displayed smaller infarct volumes than C57BL/6 | Neurotoxic | Ohtaki et al (2003) |
| Rat | |||||
| Proximal pMCAO (electrocoagulation) | SD | i.c.v. injection of 2 to 10 μg rhIL-1Ra (30 minutes before, at the time of pMCAO, and 30 minutes after pMCAO) and 2 × 2.5 ng IL-1β (30 minutes and 2 hours after pMCAO) | IL-1β treatment increased infarct volumes and body temperatures, whereas IL-1Ra treatment significantly reduced infarct volumes | Neurotoxic | Loddick and Rothwell (1996) |
| Proximal pMCAO (filament) | Wistar | i.v. injection of rhIL-1Ra at the time of occlusion followed by 3 s.c. injections during the first 24 hours after surgery | rhIL-1Ra-treated rats displayed improved neurological score and had fewer necrotic neurons and fewer leukocytes in the ischemic territory | Neurotoxic | Garcia et al (1995) |
| Proximal pMCAO (electrocoagulation) | SD | s.c. injection of 5 × 100 mg/kg rhIL-1Ra (0, 4, 8, 12, and 18 hours after pMCAO) | IL-1Ra reduced infarct volume | Neurotoxic | Relton et al (1996) |
| Proximal tMCAO (2 hours, filament) | SD | i.c.v. injection of ICE-like protease inhibitors (2 × 27 ng or 2 × 80 ng z-VAD.FMK) 15 minutes before surgery and again 10 minutes after reperfusion | ICE-like protease inhibitors reduced infarct volume | Neurotoxic | Hara et al (1997b) |
| Proximal tMCAO (1 hour, filament) | Wistar | i.c.v. injection of 10 mg rhIL-1β and 10 μg anti-IL-1β neutralizing Ab immediately after reperfusion | rhIL-1β administration increased brain edema formation and infarct size, whereas i.c.v. administration of anti-IL-1β attenuated the increase in brain water content and decreased infarct size | Neurotoxic | Yamasaki et al (1995) |
| Proximal tMCAO (1 hour, filament) | SD | i.c.v. injection of 2 × 10 μg rhIL-1Ra immediately after occlusion and again at the time of reperfusion | rhIL-1Ra-treated rats displayed decreased infarct volumes at 24 and 48 hours | Neurotoxic | Mulcahy et al (2003) |
Ab, antibody; ICE, interleukin-1β-converting enzyme; i.c.v., intracerebroventricular; IL, interleukin; IL-1RI, IL-1 receptor I; i.v., intravenous; KO, knock out; pMCAO, permanent middle cerebral artery occlusion; rh, recombinant human; s.c., subcutaneous; SD, sprague dawley; SHR, spontaneously hypertensive rats; tMCAO, transient middle cerebral artery occlusion; WT LM, wild-type littermates.