Study on therapeutic effect on collagen of rats with adjuvant arthritis lactose derivative Gu-4

Rheumatoid arthritis (RA) is a systemic, inflammatory autoimmune disorder that presents as a symmetric polyarthritis associated with swelling and pain in multiple joints. Persistent recurrent joint synovitis can lead to intraarticular cartilage and bone destruction, even finally cause disability. Recent reports suggest that the integrin CD11b/CD18or Mac-1, which is the predominant β2integrin receptor in neutrophils, macrophages and monocytes, has a central role in the resolution of inflammatory process by modulating the egress of adherent neutrophils from the site of inflammation.This implys that small molecule agonists of Mac-1may also have a role in treatment of certain inflammatory, such as rheumatoid arthritis. Our study focus on a kind of lactose derivatives Gu-4, which can effectively inhibit the adhesion and transendothelial migration of leukocytes by targeting CD11b. Early studies demonstrated that it has effects on chronic autoimmune inflammatory diseases such as endotoxin shock and sepsis. Therefore, it suggests Gu-4may have a better therapeutic effect on rheumatoid arthritis, in this study we will investigate the bioactivity of Gu-4in a rat model of CIA.CIA was induced in rats by bovine type II collagen and incomplete freund’s adjuvant. Prophylactic intervention and treatment with Gu-4(800nmol/kg given every two days, i.p) was initiated at first immunity and disease onset, respectively. The course of arthritis was monitored by plethysmometer, photographic and radiographic analyses. Histologic analyses were performed following staining with hematoxylin and eosin. The rheumatoid factor level in serum was assayed by ELISA and lymphocyte proliferation was detected via MTT essay.Finally, Gu-4significantly attenuated the severity of paw swelling and reduced arthritis score in collagen-induced arthritis rats. The infiltrate of inflammatory cells and the serum level of rheumatoid factor (RF) were degraded by Gu-4. What’s more, Gu-4inhibited the proliferation of splenic lymphocytes obtained from CIA rat in vitro.Gu-4, proved a potent antiinflammatory agent in CIA model, may have better protective and therapeutic effects on rheumatoid arthritis.