Oxaceprol, an atypical inhibitor of inflammation, reduces leukocyte adherence in mouse antigen-induced arthritis

Oxaceprol (N-acetyl-L-hydroxyproline), an atypical inhibitor of inflammatio n, is an established drug for joint disease without serious side-effects. R ecent studies have emphasized that oxaceprol has an effect on the microcirc ulation, Since the exact mechanism of action remains unclear, the aim of ou r study was to investigate the leukocyte-endothelial cell interactions in o xaceprol-treated mice with antigen-induced arthritis (AM) using intravital microscopy, In our study, Balb/c mice were allocated to 4 groups (n 7, 8, 8 , 8): 2 control groups with saline or oxaceprol and 2 groups of arthritic a nimals which received saline or oxaceprol (100 mg/kg twice a day intraperit oneally). The severity of arthritis was quantified by the transverse knee j oint diameter. For the intravital fluorescence microscopy measurements on d ay 10 after inducing arthritis, the patella tendon was partily resected to visualize the intraarticular synovial tissue of the knee joint. The number of Foiling and adherent leukocytes as well as RBC velocity and functional c apillary density (FCD) were quantified in synovial microvessels, Furthermor e, leukocyte infiltration was determined in the histological sections with an established score. No significant changes in mean arterial blood pressure or functional capill ary density were found in any of the groups. However, the leukocyte rolling fraction and number of leukocytes adherent to the endothelium were increas ed in postcapillary venules of the synovium in arthritic animals (0.16 to 0 .31, 78 cells/mm(2) to 220 cells/mm(2)). In animals with AM treated with ox aceprol, leukocyte adherence and swelling were significantly reduced in com parison to the arthritic animals treated with saline, Furthermore, the hist ological score showed less leukocyte infiltration in the oxaceproltreated a rthritic animals. Thus, oxaceprol reduces leukocyte adherence in vivo and l eukocyte infiltration in mouse AiA, indicating an effect on synovial microc irculation.