Peripheral Administration of IL-13 Induces Anti-inflammatory Microglial/Macrophage Responses and Provides Neuroprotection in Ischemic Stroke.

Abstract

Neuroinflammation is strongly induced by cerebral ischemia. The early phase after the onset of ischemic stroke is characterized by acute neuronal injury, microglial activation, and subsequent infiltration of blood-derived inflammatory cells, including macrophages. Therefore, modulation of the microglial/macrophage responses has increasingly gained interest as a potential therapeutic approach for the ischemic stroke. In our study, we investigated the effects of peripherally administered interleukin 13 (IL-13) in a mouse model of permanent middle cerebral artery occlusion (pMCAo). Systemic administration of IL-13 immediately after the ischemic insult significantly reduced the lesion volume, alleviated the infiltration of CD45+ leukocytes, and promoted the microglia/macrophage alternative activation within the ischemic region, as determined by arginase 1 (Arg1) immunoreactivity at 3 days post-ischemia (dpi). Moreover, IL-13 enhanced the expression of M2a alternative activation markers Arg1 and Ym1 in the peri-ischemic (PI) area, as well as increased plasma IL-6 and IL-10 levels at 3 dpi. Furthermore, IL-13 treatment ameliorated gait disturbances at day 7 and 14 and sensorimotor deficits at day 14 post-ischemia, as analyzed by the CatWalk gait analysis system and adhesive removal test, respectively. Finally, IL-13 treatment decreased neuronal cell death in a coculture model of neuroinflammation with RAW 264.7 macrophages. Taken together, delivery of IL-13 enhances microglial/macrophage anti-inflammatory responses in vivo and in vitro, decreases ischemia-induced brain cell death, and improves sensory and motor functions in the pMCAo mouse model of cerebral ischemia.

• Authors: Natalia Kolosowska, Meike H Keuters, Sara Wojciechowski, Velta Keksa-Goldsteine, Mika Laine, Tarja Malm, Gundars Goldsteins, Jari Koistinaho, Hiramani Dhungana
• Journal: Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics (Neurotherapeutics) Vol. 16 Issue 4 Pg. 1304-1319 (10 2019) ISSN: 1878-7479 [Electronic] United States
• PMID: 31372938 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Interleukin-13

Topics

• Administration, Intravenous
• Animals
• Anti-Inflammatory Agents (administration & dosage)
• Brain Ischemia (diagnostic imaging, drug therapy)
• Cells, Cultured
• Interleukin-13 (administration & dosage)
• Macrophages (drug effects, physiology)
• Male
• Mice
• Mice, Inbred BALB C
• Microglia (drug effects, physiology)
• Neuroprotection (drug effects, physiology)
• Stroke (diagnostic imaging, drug therapy)