Anti-type II collagen antibody and interleukin 6 in the plasma and peptidases of plasma, synovia, synovium and circulating leukocytes from rats treated with collagen type II and Apis mellifera venom

Abstract

The administration of type-II collagen in rats produces an experimental model of auto-immunity, which is well-recognized to mimic rheumatoid arthritis. 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. 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 administered with type-II collagen; 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 project intends to bring light to the study of the etiology of rheumatoid arthritis and to evaluate the effects of BV and peptidase activities as diagnostic markers and therapeutic targets of this pathology. (AU)