Development of the method in treatment of Rheumatoid Arthritis (RA) with heat-shock protein, chaperon

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Objective: to investigate the effect of intravenous BiP on the features of synovitis in rheumatoid synovial explants carried by SCID mice. Methods: Synovial membranes from patients with rheumatoid arthritis were transplanted subcutaneously into severe combined immunodeficient (SCID) mice. Intravenous BiP or human serum albumin (HSA) were administered and their effects on synovitis assessed by: comparing the weight of the explants, the histological appearance; the immunohistological presence of the co-stimulatory molecules CD86 and HLA-DR, and the circulating levels of human IL-4, IL-10 and IL-6. Results: BiP had significant suppressive effects on rheumatoid synovitis. There was reduction in the histological scoring of inflammation both by the Rooney and the Koizumi techniques. This suppression was paralleled by a decrease in the weight of the BiP-treated explants (BiP versus HSA treatment; 0.30±0.09g versus 0.37±0.11g, respectively). The expression of CD86 and HLA-DR was reduced. The circulating level of human IL-6 was reduced to background levels. When a human anti-IL-10 monoclonal antibody was administered to the mice prior to BiP injection, there was a significant reversal of the weight reducing effect of BiP on the explants. Conclusion: BiP is able to reverse histological and immunohistological features of rheumatoid synovitis as well as circulating human IL-6 levels in SCID mice bearing rheumatoid explants and suggests that BiP should be trialed as a therapeutic agent in RA.