MCP-I expression by astrocytes, perivascular cells, infiltrating monocytes, and endotbelial cells during the course of IL-1-induced inflammation of the CNS

Monocyte chemotactic peptide-1 (MCP-1) is a member of the C-C family of chemokines and is primarily responsible for the recruitment of monocytes and activated T cells during an inflammatory response. MCP-1 has been implicated in the pathogenesis of several diseases including experimental autoimmune encephalomyelitis, an animal model for the demyelinating disease multiple sclerosis. Several cell types in the central nervous system (CNS) express MCP-1 following 1L-1 or TNF treatment in vitro; however, the regulation of this chemokine in vivo is unknown. We employed in situ hybridization to determine the kinetics and cellular sources of MCP-1 expression during the course of IL-1-induced inflammation of the CNS. Injection of IL-1 into the vitreous of the rabbit eye induced inflammation of the retina that consisted of monocyte and neutrophu accumulation commencing 3h post intra-ocular challenge (PIC) and peaking at 24h PIC. MCP-1 mRNA was detected as early as 2h PIC, remained at essentially the same level at 3h PIC, and increased at both 6 and 24h PIC. Astrocytes and perivascular cells were the primary sources of MCP-1 mRNA. Infiltrating mononuclcar cells, but not polymorphonuclear cells, also produced MCP-1. Endothelial cells expressed MCP-1 message only at 24h PIC, the peak of the response. These data suggest that the expression of MCP-1 by cells in a perivascular location may provide a chemotactic gradient necessary for the recruitment of monocytes during inflammation of the CNS. Additionally, the kinetics of EC-derived MCP-1 expression suggests a suppressive role in this process, perhaps bv disruption of the chemotactic gradient.