Anti-very late antigen-1 monoclonal antibody modulates the development of secondary lesion and T-cell response in experimental arthritis

Rats injected in the hind paw with a mixture of Mycobacterium butirricum em ulsified in mineral oil (FA) developed a severe polyarthritis that shared s ome immunological features with human rheumatoid arthritis. After this loca l administration, rats developed a secondary lesion (edema) in the contrala teral paw, which is a hallmark of immune system activation. In vivo intrave nous treatment with a monoclonal anti-very late antigen (VLA)-1 antibody (H A31/8) significantly reduced the edema formation in the contralateral paw. T cells isolated from contralateral paw draining lymph nodes of FA rats tre ated with HA31/8 showed a reduced cell proliferation in vitro, after stimul ation with concanavalin A. Furthermore FAGS analysis showed that the reduct ion in proliferation was concomitant to a reduction in the number of T cell s positive to surface IL-2 receptor expression. Our data indicate that afte r in vivo treatment with a monoclonal anti-very late antigen-1 antibody, th ere is a beneficial effect on the development of the secondary lesion, whic h correlates to the reduced ability of T cells to proliferate in vitro as w ell as to a reduced surface expression of IL-2 receptor. The association of this antibody to other drugs interfering at other levels in rheumatoid art hritis may open a new therapeutic window.