School of Biological Sciences, University of Manchester, Manchester, U.K.

Correspondence: Christine A Davies, School of Biological Sciences, 1.124 Stopford Building, University of Manchester, Manchester M13 9PT, U.K.

Received 26 February 1998; Revised 7 April 1998; Accepted 7 April 1998.

Abstract

The cytokine interleukin-1 (IL-1) has been implicated in the exacerbation of ischemic damage in the brains of rodents. This study has ascertained the cellular localization and chronologic and topographic distribution of pro/mature interleukin-1 (IL-1) protein 0.5, 1, 2, 6, 24, and 48 hours after ischemia by subjecting rats to permanent unilateral occlusion of the middle cerebral artery. Interleukin-1 was localized immunocytochemically in vibratome sections of perfusion-fixed brains. The cells that expressed IL-1 had the morphologic features of microglia and macrophages. Interleukin-1 was first detected 1 hour after occlusion in ipsilateral meningeal macrophage-like cells. By 6 hours, pro/mature IL-1-immunoreactive (IL-1ir) putative microglia were present in the ischemic cerebral cortex, corpus callosum, caudoputamen, and surrounding tissue. By 24 and 48 hours after ischemia, the number and spread of IL-1ir cells increased greatly, including those resembling activated microglia and macrophages, as the core of the infarct became infiltrated. Interleukin-1ir cells also were present in apparently undamaged tissue, adjacent to the lesion ipsilaterally, and contralaterally in the cerebral cortex, dorsal corpus callosum, dorsal caudoputamen, and hippocampus. These results support the functional role of IL-1 in ischemic brain damage and reveal a distinct temporal and spatial expression of IL-1 protein in cells believed to be microglia and macrophages.