Involvement of endogenous tumor necrosis factor alpha and transforming growth factor beta during induction of collagen type II arthritis in mice.

Abstract

Both tumor necrosis factor a (TNF-a) and transforming growth factor 13 (TGF-1) are found in synovial fluid from arthritic joints of humans and of rodents with experimental arthritis. The role of endogenously produced TGF-fi and TNF in the pathogenesis of collagen type U-induced arthritis (CIA) in DBA/1 mice was examined by determining the effect of neutralizing monoclonal antibodies to these factors on the course of the disease. Endogenously produced as well as systemically administered TGF-P1 and TNF-a had opposite effects, since TGF-(31 and anti-TNF protected against CIA, whereas anti-TGF-fi and TNF-a increased CIA incidence and/or severity. Intraperitoneally Injected TGF-13 at a dose of 2 pg per day for 14 days signficantly ameliorated arthritis, even when started at the time of arthritis development, although it did not reverse established disease. The resistance to CIA induction caused by a prior intravenous injection of collagen type H was not significantly influenced by the simultaneous injection of TGF-,13, TNF-a, or interleukin la. It is concluded that the endogenous production of TNF and TGF-1 is important in determining the course of CIA.

RETRACTED: Cloricromene, a coumarine derivative, protects against collagen‐induced arthritis in Lewis rats

“…In vitro, TNF is also less potent Berg et al, 1994;Williams et al, 1992;Piguet et al, 1992;Thorbecke et al, 1992).…”

Dynamic expression of transforming growth factor-betas (TGF-β) and their type I and type II receptors in the synovial tissue of arthritic rats

“…To date, it has been shown that systemic administration of TGF-1 to rodents protects against induction of arthritis [12,13] and experimental allergic encephalomyelitis (EAE) [37][38][39][40]. It has also been demonstrated that TGF-2 is as effective as TGF-1 in protecting against EAE [40,41], thus indicating that these TGF-s have similar biological effects in EAE.…”

“…Several studies have demonstrated the presence of TGF-in the synovium and synovial fluids of RA patients [5][6][7][8][9][10][11]. In rodents, conversely, the action of TGF-or its antagonists administered in vivo in experimental arthritis has been intensively studied [12,13]. However, in the animal arthritis models, little is known concerning both the distribution and the kinetics of the different isoforms of TGF-and its receptors [8].…”

Treatment with a neutralizing anti‐murine interleukin‐17 antibody after the onset of collagen‐induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion

“…The proinflammatory cytokines TNF␣ and IL-1␤ play a crucial role in the pathology of arthritis, driving enhanced production of cytokines, chemokines, and degradative enzymes (12). In vivo studies have shown that neutralizing TNF␣ or IL-1␤ controls chronic inflammation and cartilage degradation, respectively (13)(14)(15). Consistent with this, clinical studies revealed efficacy after blocking of TNF␣ or IL-1␤.…”