Effects of Apis mellifera venom on anti-type II collagen antibody, interleukin 6 and peptidases of synovia, synovium and circulating leukocytes in rats with type-II collagen-induced arthritis

Abstract

Rheumatoid arthritis affects about 1% of the worldwide population. It is characterised by cellular infiltration in the synovium, progressive erosion of cartilage and bone and pannus formation in the affected joints, as well the immune response to cartilage components and the presence of rheumatoid factors. Several mechanisms are involved in the disease establishment and chronicicity, as the activation of macrophages, neutrophils, linfocytes T and B and dendritic cells, formation of immune complexes, angiogenesis and release of cytokines and chemokines. The bee venom therapy has been used in oriental medicine to treat inflammatory diseases, as rheumatoid arthritis, by its property to decrease pain and inflammation. Moreover, the destruction of cartilage, inflammatory mechanisms and antigenic processing are related to aminopeptidases, such as neutral (APN), basic (APB) and dipeptidyl-peptidase IV, and to prolyl oligopeptidase (POP). The aims of the present project are to analyse: (1) the involvement of APN, APB, DPP-IV and POP activities in the plasma, synovia and synovium, as well in mononuclear and polymorphonuclear cells, ex vivo and in vitro, in rats with type-II collagen-induced arthritis; and (2) if changes on the levels of these peptidase activities and inflammatory markers, such as anti-type II collagen antibody and interleukin (IL)-6, could be mitigated after treatment with Apis mellifera venom (BV) and/or methotrexate (MTX) (commonly used drug for rheumatoid arthritis). This study intends to bring light to the etiology of rheumatoid arthritis and to evaluate the anti-arthritic effects of BV and peptidase activities as diagnostic markers and therapeutic targets of this pathology.