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: Isabel Pérez-de Puig, Francesc Miró, Angélica Salas-Perdomo, Ester Bonfill-Teixidor, Maura Ferrer-Ferrer, Leonardo Márquez-Kisinousky, Anna M Planas
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 33 Issue 12 Pg. 1955-66 (Dec 2013) ISSN: 1559-7016 [Electronic] United States
• PMID: 24022622 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Interleukin-10
• Interleukin-10

Topics

• Animals
• Brain (blood supply, immunology, metabolism, pathology)
• Brain Edema (genetics, immunology, pathology)
• Gene Knockout Techniques
• Infarction, Middle Cerebral Artery (genetics, immunology, pathology)
• Inflammation (genetics, immunology, pathology)
• Interleukin-10 (genetics, immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Receptors, Interleukin-10 (genetics)
• Up-Regulation