To examine whether chemokine antagonists inhibit the initiation and progression of lupus nephritis in MRL/lpr mice.

NH₂‐terminal–truncated monocyte chemoattractant protein 1 (MCP‐1)/CCL2 or thymus and activation–regulated chemokine (TARC)/CCL17 analogs were inserted into the pCXN2 expression vector and transfected into a nonmetastatic fibroblastoid cell line, MRL/N‐1, established from an MRL/gld mouse.

MCP‐1 antagonist– or TARC antagonist–transfected MRL/N‐1 cells were injected subcutaneously into MRL/lpr mice ages 7 weeks (before the onset of lupus nephritis) and 12 weeks (at the early stage of the disease). After 8 weeks, mice bearing the MCP‐1 antagonist showed markedly diminished infiltration of macrophages and T cells, glomerular hypercellularity, glomerulosclerosis, crescent formation, and vasculitis compared with control mice. This seemed to be due to decreased production of interferon‐γ and interleukin‐2 in the kidney. In contrast, there was no significant difference in renal damage between mice bearing TARC antagonist and control mice.

We established a new system using MRL/N‐1 cells that allows long‐term observation of the effects of chemokine antagonists on lupus nephritis in MRL/lpr mice. We also showed that the MCP‐1 antagonist ameliorated the initiation and progression of lupus nephritis and of renal vasculitis, which might provide a new approach to the treatment of the disease.