title: IL-10 deficiency exacerbates the brain inflammatory response to permanent ischemia without preventing resolution of the lesion.
abstract: Stroke induces inflammation that can aggravate brain damage. This work examines whether interleukin-10 (IL-10) deficiency exacerbates inflammation and worsens the outcome of permanent middle cerebral artery occlusion (pMCAO). Expression of IL-10 and IL-10 receptor (IL-10R) increased after ischemia. From day 4, reactive astrocytes showed strong IL-10R immunoreactivity. Interleukin-10 knockout (IL-10 KO) mice kept in conventional housing showed more mortality after pMCAO than the wild type (WT). This effect was associated with the presence of signs of colitis in the IL-10 KO mice, suggesting that ongoing systemic inflammation was a confounding factor. In a pathogen-free environment, IL-10 deficiency slightly increased infarct volume and neurologic deficits. Induction of proinflammatory molecules in the IL-10 KO brain was similar to that in the WT 6 hours after ischemia, but was higher at day 4, while differences decreased at day 7. Deficiency of IL-10 promoted the presence of more mature phagocytic cells in the ischemic tissue, and enhanced the expression of M2 markers and the T-cell inhibitory molecule CTLA-4. These findings agree with a role of IL-10 in attenuating local inflammatory reactions, but do not support an essential function of IL-10 in lesion resolution. Upregulation of alternative immunosuppressive molecules after brain ischemia can compensate, at least in part, the absence of IL-10.
authors.affiliation: 1] Departament d'Isquèmia Cerebral i Neurodegeneració, Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain [2] Area of Neurosciences, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Pérez-de Puig
authors.forename: Francesc
authors.initials: F
authors.lastname: Miró
authors.forename: Angélica
authors.initials: A
authors.lastname: Salas-Perdomo
authors.forename: Ester
authors.initials: E
authors.lastname: Bonfill-Teixidor
authors.forename: Maura
authors.initials: M
authors.lastname: Ferrer-Ferrer
authors.forename: Leonardo
authors.initials: L
authors.lastname: Márquez-Kisinousky
authors.forename: Anna M
authors.initials: AM
authors.lastname: Planas
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D001929:Brain Edema / Q000235:genetics / Q000276:immunology / Q000473:pathology; D055786:Gene Knockout Techniques; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053701:Receptors, Interleukin-10 / Q000235:genetics; D015854:Up-Regulation
chemical_list: D053701:Receptors, Interleukin-10; D016753:Interleukin-10
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