Expert Opin Ther Targets 2003 Feb;7(1):35-48
Dawson J, Miltz W, Mir AK, Wiessner C.
Arthritis and Bone Metabolism Research, Novartis Pharma AG, Basel, Switzerland.
Monocyte chemoattractant protein-1 (MCP-1) has been implicated in many inflammatory and autoimmune diseases.
The G-protein-coupled receptor CCR-2B is probably the most important MCP-1 receptor in vivo, and loss of MCP-1 effector function alone is sufficient to impair monocytic trafficking in inflammation models.
MCP-1 signalling appears to be a relevant target, especially in rheumatoid arthritis (RA).
In RA patients, MCP-1 is produced by synovial cells and infiltrating monocytes, plasma MCP-1 concentrations correlate with swollen joint count, and elevated serum MCP-1 concentrations were found in juvenile RA in patients with active disease.
Modulation of MCP-1 signalling in experimental RA showed beneficial effects on inflammation and joint destruction.
With respect to chronic neuroinflammation, a critical role for MCP-1 has been established in animal models for multiple sclerosis.
In acute neuroinflammation, experimental evidence for a detrimental role of MCP-1 in stroke and excitotoxic injury has been found.
Several selective small molecular weight CCR-2B antagonists and MCP-1-blocking antibodies have been described.
The proof for the validity of targeting MCP-1 signalling in disease, however, has yet to be established in clinical trials.