Effects of ibandronate on inflammation in mouse antigen-induced arthritis

Objective: To investigate the effects of ibandronate, a novel aminobisphosphonate, on inflammation as well as leukocyte-endothelial cell interaction in mouse antigen-induced arthritis (AiA). Material and Treatment: 36 Balb/c mice were subcutaneously injected with 160 μg/kg of ibandronate once per day beginning at day 7 until day 13 after induction of AiA. Methods: The severity of arthritis was assessed by changes of the transverse knee joint diameter. For the intravital fluorescence microscopy measurements on day 14 after AiA induction, the patella tendon was partly resected to visualize the intraarticular synovial tissue of the knee joint. The number of rolling and adherent leukocytes as well as red blood cell (RBC) velocity and functional capillary density (FCD) were quantified in synovial microvessels. Furthermore, leukocyte infiltration in the synovium was determined in histological sections with an established score. Results: Both fractions of rolling leukocytes (p = 0.016) as well as number of extravasated leukocytes (p = 0.004) were enhanced in control animals treated with ibandronate in comparison to animals which received saline. Arthritic animals with and without ibandronate treatment revealed an increased FCD (p = 0.006, p = 0.008), enhanced number of rolling ( p = 0.002, p = 0.001) and adherent leukocytes (p = 0.009, p = 0.007) and greater swelling of the left knee joint (p = 0.002, p = 0.001) when compared to control animals. No significant differences between arthritic animals and arthritic animals treated with ibandronate were found in any of the parameters assessed including leukocyte adherence, FCD, histology, and knee joint swelling. Conclusion: Ibandronate treatment of healthy mice was associated with an enhanced fraction of rolling leukocytes and increased numbers of extravasated leukocytes indicating a proinflammatory effect on the synovial microcirculation. In animals with a preexisting antigen-induced arthritis, however, ibandronate did not induce an exacerbation of joint inflammation and leukocyte adherence.