Rheumatoid arthritis adjuvant-induced

MTX is part of curative therapeutic schedules for acute lymphoblastic leukemias (ALL), Burkitt s lymphoma, and choriocarcinoma. It was also used in adjuvant therapy of breast cancer. High dose MTX with leucovorin rescue can induce about 30% remissions in patients with metastatic osteogenic sarcoma. MTX is one of the few antineoplastic drugs that can be safely administered intrathecally for the treatment of meningeal metastases and leukemic infiltrations (routine prophylaxis in ALL). In addition, MTX can be used as an immunosuppressive agent for the treatment of severe rheumatoid arthritis and psoriasis. 

Holmdahl R, Lorentzen JC, Lu S, et al. Arthritis induced in rats with nonimmunogenic adjuvants as models for rheumatoid arthritis. Immunol Rev 2001 184 184-202. 

Ruth JH, Volin MV, Haines GK 3rd, et al. Fractalkine, a novel chemokine in rheumatoid arthritis and in rat adjuvant-induced arthritis. Arthritis Rheum 2001 44(7) 1568—1581. 

Ochaion A, Bar-Yehuda S, Cohen S, Amital H, Jacobson KA, Joshi BV, Gao ZG, Barer F, Patoka R, Del Valle L, Perez-Liz G, Fishman P (2008) The A3 adenosine receptor agonist CF502 inhibits the PI3K, PKB/Akt and NF-kappaB signaling pathway in synoviocytes from rheumatoid arthritis patients and in adjuvant-induced arthritis rats. Biochem Pharmacol... 

Fishman P, Bar-Yehuda S, Madi L, Rath-Wolfson L, Ochaion A, Cohen S, Baharav E (2006) The PI3K-NF-K B signal transduction pathway is involved in mediating the anti-inflammatory effect of IB-MECA in adjuvant-induced arthritis. Arthritis Res Ther 8(1) 1-9 Goldbach-Mansky R, Lipsky PE (2003) New concepts in the treatment of rheumatoid arthritis. Annu Rev Med 54 197-216... 

Fishman P (2008) Clinical evidence for utilization of the A3 adenosine receptor as a target to treat rheumatoid arthritis data from a phase II clinical trial. J Rheumatol 35(1 ) 41—48 Sizova L (2008) Approaches to the treatment of early rheumatoid arthritis with disease-modifying antirheumatic drugs. Br J Clin Pharmacol 66(2) 173-178 Spargo LD, Cleland LG, Cockshell MP, Mayrhofer G (2006) Recruitment and proliferation of CD4+ T cells in synovium following adoptive transfer of adjuvant-induced arthritis. Int Immunol 18(6) 897-910... 

Levamisole was first synthesized for the treatment of parasitic infections. Later studies suggested that it increases the magnitude of delayed hypersensitivity or T cell-mediated immunity in humans. In immunodeficiency associated with Hodgkin s disease, levamisole has been noted to increase the number of T cells in vitro and to enhance skin test reactivity. Levamisole has also been widely tested in rheumatoid arthritis and found to have some efficacy. However, it has induced severe agranulocytosis (mainly in HLA-B27-positive patients), which required discontinuation of its use. The drug may also potentiate the action of fluorouracil (5-FU) in adjuvant therapy of colorectal cancer, and this combination has been approved for clinical use in the treatment of Dukes class C colorectal cancer after surgery. Its use in these cases reduces recurrences, and the mechanism... 

Shiojiri, T., Wada, K., Nakajima, A., Katayama, K., Shibuya, A., Kudo, C., Kadowaki, T., Mayumi, T., Yura, Y., and Kamisaki, Y. (2002). PPAR gamma ligands inhibit nitrotyrosine formation and inflammatory mediator expressions in adjuvant-induced rheumatoid arthritis mice. Eur.J. Pharmacol. 448, 231-238. 

Bisphosphonates (particularly clodronate) have been shown to have anti-inflammatory effects in animal models of rheumatoid arthritis (RA), as well as in arthritis in humans. In adjuvant- and antigen-induced arthritis in rats, clodronate suppresses the inflammatory articular lesions in the inflamed joints [29], whilst in human RA, clodronate decreases the levels of interleukin (ILJ-1, tumor necrosis factor-alpha (TNFaand /1-microglobulin in the circulation [30]. In vitro, clodronate inhibits cytokine and nitric oxide (NO) release and inducible nitric oxide synthase (iNOS) expression in macrophage-like cells. 

Models of rheumatoid arthritis (RA) were object to l,25(OH)2D3 treatment, providing additional support for the high potential of the hormone for the treatment of Thl-mediated diseases. As an example, in rat adjuvant arthritis l,25(OH)2D3 improved the inhibiting effect of cyclosporine A on arthritis onset as well as on arthritis aggravation [142]. The incidence and severity of type II collagen-induced arthritis was reduced in rats or mice orally treated with 25-(OH)2-D3, the 1,25 (OH)2D3 analog MC 1288 or l,25(OH)2D3 [143-145], l,25(OH)2D3 has further proven to be therapeutically effective in animal models of autoimmune thyroiditis [146], allogeneic transplantation [66, 147,148], rat Heymann nephritis [149] and autoimmune prostatitis [80]. Results from l,25(OH)2D3-related studies in animal models are summarized in Table 10.3. 

In contradistinction to the various types of chemically-induced and anaphylactic arthritis which have been mentioned above, adjuvant arthritis appears to simulate closely the inflammatory reactions seen in rheumatoid arthritis in humans. Stoerk, Bielinski and Budzilovitch first reported the development of a chronic polyarthritis in rats, and this work was later elaborated by a number of other workers " . The reaction seems to be a type of delayed hypersensitivity response , although recent work suggests that this may not be so. ... 

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