Suppression of @entity1753 by an angiogenesis inhibitor, @entity10822 , in combination with @entity205 : reduction of @entity6667 ( XXXX ).

@entity625 @entity870 @entity10822 @entity11264 @entity1505 @entity1753 @entity2070 @entity205 @entity5041 @entity56 @entity35 @entity6667 @entity309
@entity2070 formation characterized by neovascularization is a prominent pathologic finding in both @entity309 ( @entity309 ) and @entity35 @entity1753 ( @entity1753 ). @entity1753 is a T-cell-dependent process induced by immunization of inbred LOU @entity35 with native type II collagen in incomplete Freund's adjuvant. @entity10822 is a highly specific inhibitor of new blood vessel formation by its effects on endothelial cell migration, endothelial cell proliferation, and capillary tube formation. @entity205 ( @entity870 ) is an immunomodulating agent that inhibits @entity5041 and other cytokine production involved in early antigen activation of T-cells. In this study the effects of single and combination therapy with @entity10822 (27 mg/kg alternate days) and low-dose @entity870 (4 mg/kg/day continuous infusion via osmotic pump) on established @entity1753 (total n = 62) were examined. At Day 18 post @entity625 onset, clinical @entity625 was significantly reduced in @entity35 treated with single-agent @entity10822 (1.88 +/- 0.33) or combination therapy (1.13 +/- 0.32) (P < 0.00001 and 0.000001, respectively) versus control. Single-agent @entity870 -treated @entity35 , even if given @entity870 beginning on the day of immunization, did not attenuate @entity625 severity. THe @entity625 score of combination-treated @entity35 was significantly lower than that of @entity35 receiving @entity10822 (P < 0.0001), reflecting a more moderate early disease course in combination-treated @entity35 . Disease severity in @entity35 treated with single-agent @entity870 was not significantly different from control @entity35 . Mean WBC counts, differentials, and @entity56 responses were similar in all groups. CII antibody levels were lower in @entity10822 protocols compared to @entity870 or controls. Flow cytometry of peripheral blood, spleen, and lymph nodes demonstrated decreased levels of @entity11264 + cells in @entity35 given @entity870 . @entity1505 levels remained elevated, even in treated @entity35 , while @entity6667 levels were reduced in @entity35 receiving @entity10822 compared to both arthritic controls and naive @entity35 . Both single-agent and combination therapies were well tolerated. This is the first study to examine the effects of @entity10822 together with @entity870 . Combination therapy was more effective than single-agent therapy. The results suggest that the use of interventions with distinct mechanisms of action may be efficacious in the treatment of @entity309 .
