Studies in mice with induced arthritis suggest that the human complement inhibitor C4b-binding protein (C4BP) may be of use in the treatment of rheumatoid arthritis, Swedish researchers report in the January issue of the Annals of the Rheumatic Diseases.
"The complement system is inappropriately activated in rheumatoid arthritis," lead investigator Dr. Anna M. Blom told Reuters Health, "and a number of studies suggest that complement inhibitors could be used to treat this disease."
To investigate further, Dr. Blom of Lund University, Malmo, and colleagues used two mouse models of arthritis -- collagen antibody-induced arthritis (CAIA), an acute antibody-induced disease, and collagen-induced arthritis (CIA), "which carries the full complexity of arthritis."
Intraperitoneal injection of purified human C4BP led to a significant alleviation of CAIA, similar to that prompted by cobra venom factor, an agent that depletes complement factor via massive activation.
When C4BP was injected into CIA mice before disease development, onset was delayed. When injected after development, it reduced disease severity but did not affect anti-collagen type II antibody synthesis. It thus decreased classical but not alternative pathway activity.
"Complete depletion of complement may cause adverse side effects such as increased susceptibility to infections," continued Dr. Blom, "but we have now demonstrated that even partial inhibition of complement can measurably decrease the activity of CIA and CAIA in mice."
The findings, she concluded, "further strengthen the idea of developing complement inhibitors to treat rheumatoid arthritis."
Ann Rheum Dis 2009;68:136-142.