Monocyte chemoattractant protein-1 activates a regional Th1 immuno-response in nephritis of MRL/lpr mice

Objective. Monocyte chemoattractant protein-1 (MCP-1) is upregulated and recruits and activates inflammatory cells in nephritis of MRL lpr mice. It has been shown that anti-MCP-1 gene therapy is specifically effective in nephritis, while it was apparent that an imbalance towards Th1 predominance accelerates nephritis in MRL/lpr mice. The aim of this study was to clarify whether blockade of the MCP-1 signal by anti-MCP-1 gene therapy influences the Th1/Th2 balance in MRL/lpr mice. Method. An NH2-terminal deletion mutant of the MCP-1 gene (7ND) was injected into the skeletal muscles of MRL/lpr mice with advanced stage nephritis to suppress MCP-1 and its receptor (CCR2) signaling pathway. We evaluated the local tissue product. on of cytokines in splenocytes and microdissected infiltrating cells within the glomeruli or interstitium. Result. Although the production of cytokines in splenocytes was not influenced by anti-MCP-1 gene therapy, kidney glomeruli IL-12 mRNA product on and interstitium-infiltrating cell production of IL-12 and IFN-gamma mRNA were significantly reduced. Conclusion. The blockade of MCP-1 gene therapy does not influence helper T cell polarization, but acts directly on the regional Th1 immunoreaction in MRL/lpr mice.