Effect Of Combination Methotrxate And Cyclophosphamide Intermitently Therapy On Symptom And Serum IL-1,TNF-α In Collagen-Induced Arthritis Rats

BackgroundRheumatoid arthritis is a mutilation autoimmune disease.Cytokines play important effects on enlarging immunologic derangement and joints destroy.IL-1 and TNF-a are representative cytokines,who make joints chronic symmetry corrodibility change and vasculitis.General treatments have no obvious effects,or have many side effects,or drugs are expensive. Combination methotrxate and cyclophosphamide intermitently therapy according cell cycle can improve effects efficaciously and decrease the side effects.ObjectiveInvestigate the effect of combination methotrexate(MTX)and Cyclophosphamide(CTX) intermitently therapy on collagen-induced arthritis Rats.Investigate its possible synergistic effect and evaluate the possible mechanisms through the arthritis index,arthritis swelling degree and the serum IL-1,TNF-α.Methods1.90 Wistar rats were raised,received two times mixed liquor of cattleⅡcollagen and Freund's complete adjuvant(CFA)by endermic injection.CIA rats were made.2.75 CIA rats were divided to 5 groups randomly,and received combination MTX and CTX treatment or other kinds control drugs respectively.Rats received different treatments for 24 weeks.3.Observe the change of arthritis index,arthritis swelling degree,and appearance of imageology and pathology.Take blood,separate and obtain serum,detected the serum IL-1,TNF-αby enzyme-linked immunosorbentassay.Results1.Arthritis index,arthritis swelling degree,and appearance of imageology and pathology are labels,75 rats who had received mixed liquor of cattleⅡcollagen and CFA happened symmetry polyarthritis,achievement ratio of model is 83.3%;2.0.9mg/kg/w and 2.7mg/kg/w MTX can inhibit the appearance of arthritis and serum IL-1,TNF-αof CIA rats,the difference has statistics meaning.24mg/kg/21d CTX has the same effects.Combination 0.9mg/kg/w MTX and 24mg/kg/21d CTX can inhibit arthritis index, arthritis swelling degree,and serum IL-1,TNF-αof CIA rats obviously,the difference between combined drugs and separately drugs has statistics meaning(P＜0.05).3.Combination 0.9mg/kg/w MTX and 24mg/kg/21d CTX treatment and 2.7mg/kg/w MTX treatment have synergistic effect in inhibiting arthritis index,arthritis swelling degree,and serum IL-1,TNF-αof CIA rats(P＜0.05),there is no statistics difference(P＞0.05).Conclusions1.MTX and CTX have synergistic effect in inhibiting arthritis index,arthritis swelling degree,and serum IL-1,TNF-αof CIA rats;2.Combination lower-dosage MTX and CTX have the same effect comparing with treatment high-dosage MTX in inhibiting arthritis index,arthritis swelling degree,and serum IL-1,TNF-αof CIA rats.