LOW-DOSE METHOTREXATE DECREASES INTRAARTICULAR PROSTAGLANDIN AND INTERLEUKIN-1 LEVELS IN ANTIGEN-INDUCED ARTHRITIS IN RABBITS

Objective. To investigate the effects of methotrexate (MTX) on inflamm ation variables of antigen induced arthritis (ATA) in rabbits, such as protein leakage to the articular cavity, synovial fluid (SF) leukocyt e count, synovial membrane polymorphonuclear (PMN) cell infiltrate, an d intraarticular production of eicosanoids and interleukin 1 (IL-I). D examethasone and indomethacin were used for comparison. Methods. NZW r abbits were treated with the following drugs: MTX (0.25 mg/kg), dexame thasone (0.15 mg/kg), indomethacin (4 mg/kg), and sterile saline (cont rol group). All drugs were given by intramuscular route before arthrit is was induced and the animals were sacrificed 4 or 24 h later, Leukoc yte migration, protein leakage (Evans blue method), synovium PMN cell infiltrate, and intraarticular concentration of prostaglandin E(2) (PG E(2)), thromboxane B-2 (TXB(2)), leukotriene B-4 (LTB(4)) (radioimmuno assay), and IL-1 beta (ELISA) were quantified in SE Results. Significa nt reduction of leukocyte migration and protein leakage was observed i n the joint fluid of all treated animals. Decrease in the intensity of synovium PMN cell infiltrate also occurred with all treatments. Intra articular PGE(2), TXB(2), and IL-1 beta were significantly reduced aft er 4 h of arthritis induction in animals treated with MTX and dexameth asone. Treatment with indomethacin reduced only PGE(2) and TXB(2) in S E Treatments did not change SF IL-1 beta concentration 24 h after arth ritis induction. Treatment with dexamethasone increased inflammatory v ariables and SF LTB(4) concentration 24 h after the synovial cavity wa s challenged with antigen. Conclusion, Our results show that MTX, like dexamethasone, reduces the intensity of leukocyte afflux, protein lea kage, synovial membrane PMN cell infiltrate, as well as the intraartic ular production of PGE(2), TXB(2), and IL-1 beta in the early phase of antigen induced arthritis in rabbits.