ANTIARTHRITIC EFFECT OF IMMUNOMODULATOR DERINAT ALONE AND IN COMBINATION WITH METHOTREXATE ON ADJUVANT ARTHRITIS IN RATS

Background: Treatment of rheumatoid arthritis (RA) remains a complicated problem, therefore it is very important to search for the new drugs and their combinations with common preparations, e.g. methotrexate (MTX), widely used for the treatment of RA (1). Derinat (D), a bioactive substance, has been extracted from sturgeon milt (2). It is a native DNA-sodium diluted in 0.1% saline solution and possesses immunomodulatory properties.Objectives: To evaluate and compare the antiarthritic effect of D alone and in combination with MTX using the rat adjuvant arthritis (AA) as a model of RA.Methods: Experiment was performed on 60 male Wistar rats with AA. D in doses 6 mg/kg (1st gr.) and 18 mg/kg (2nd gr.) was given alone and in combination with MTX (2 mg/kg) (3rd and 4th gr.) and compared with MTX alone (5th gr.). Control group (6th) received 0.85% NaCl. D was injected intramuscularly (i.m.) 5 times a week and MTX - i.m. once a week. Treatment was started simultaneously with AA and lasted 17 days. Body weight and joint swelling were checked 3 times a week. Hematological, immunological and pathomorphological changes were evaluated at the end of experiment.Results: Both doses of D (6 mg/kg and 18 mg/kg) significantly reduced joint swelling by 29-69% and 20-48% respectively. The lower dose of D was more effective than MTX (P<0.05-0.01). Combined treatment also significantly suppressed joint swelling but didn't appeared more effective than MTX alone. Polyarthritis developed in 10% animals of 1st and 4th gr., 20% - of 2nd gr., and 40% of control group. It was absent in 3rd and 5th groups. All kinds of treatment markedly diminished ESR and count of leukocytes (P<0.01-0.001). The latter was the most suppressed (by 48.3%) after the treatment with MTX. The level of TNF-alfa was decreased by 46.6% (P<0.01) and 23.6% under the therapy with D in doses 6 mg/kg and 18 mg/kg respectively. Combined therapy reduced TNF-alfa by 9.8% and 12.2% but it decreased the toxicity of MTX on liver. Blasttransformation of lymphocytes to PHA was the most expressed (P<0.001) under the treatment with D (6 mg/kg) and increased by using MTX+D in comparison with control group. Pathomorphological changes in joints significantly improved under the treatment with D and its combination with MTX and no essential differences from MTX alone were observed, except the fibrosis in synovium which was milder in the 1st group treated with D, and inflammatory infiltration with macrophages which was weaker in MTX group.Conclusion: D alone and in combination with MTX was well tolerated and suppressed AA. The low doses of D possessed the most marked antiinflammatory and antiarthritic effect. Combination of D+MTX diminished the toxic effect of MTX on liver and the count of leukocytes.1. Rudwaleit M, Yin Z, Siegert S, et al. Response to methotrexate in early rheumatoid arthritis is associated with a decrease of T cell derived tumour necrosis factor alfa, increase of interleukin 10, and predicted by the initial concentration of interleukin 4. Ann Rheum Dis 2000; 59:311-4.2. Kaplina EN. The employment of of preparation Derinat in various spheres of medicine. Materials of Conference. Moscow 2000; 1-50.1. Rudwaleit M, Yin Z, Siegert S, et al. Response to methotrexate in early rheumatoid arthritis is associated with a decrease of T cell derived tumour necrosis factor alfa, increase of interleukin 10, and predicted by the initial concentration of interleukin 4. Ann Rheum Dis 2000; 59:311-4.2. Kaplina EN. The employment of of preparation Derinat in various spheres of medicine. Materials of Conference. Moscow 2000; 1-50.Citation: , volume , supplement , year 2002, page Session: Rheumatoid arthritis – Etiology and pathogenesis/Animal models 2