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Rheumatology 1999; 38: 984-991
© 1999 British Society for Rheumatology

Pro-inflammatory effects of the aminobisphosphonate ibandronate in vitro and in vivo

P. J. Richards, N. Amos, A. S. Williams and B. D. Williams

Rheumatology Research Laboratory, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, UK

Correspondence to: P. J. Richards, Rheumatology Research Laboratory, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, UK.

Objectives. To investigate the effects of the aminobisphosphonate, ibandronate, on the course of joint inflammation in rat antigen-induced arthritis (AIA) and the release of pro-inflammatory cytokines in partially purified human peripheral blood mononuclear cells (PBMC).

Methods. Rats with AIA received a single intra-articular injection of ibandronate (1 mg) 7 days post-arthritis induction and knee swelling was measured for 7 days thereafter. The effects of ibandronate (300 µg/ml) on PBMC cytokine production and activation marker expression were determined using polymerase chain reaction (PCR)/ELISA and FACS analysis, respectively.

Results. Joint swelling, associated with AIA, was sustained in ibandronate-treated rats compared with saline-treated control rats. Ibandronate stimulated the production of interferon gamma (IFN-{gamma}) in adherent PBMC, and increased the surface expression of Fc{gamma}RI and HLA DP, DQ, DR on the adherent monocyte population. Activation by lipopolysaccharide (LPS) of PBMC previously incubated with ibandronate led to enhanced levels of tumour necrosis factor alpha (TNF-{alpha}) secretion, and this could be partially inhibited by neutralizing antibodies to IFN-{gamma}.

Conclusions. The enhanced production of TNF-{alpha} by ibandronate-treated PBMC in vitro involves stimulation of adherent monocytes by IFN-{gamma} prior to LPS-induced activation. Similar cellular interactions may be involved in the pro-inflammatory effects of ibandronate in vivo.

KEY WORDS: Ibandronate, Antigen-induced arthritis, Tumour necrosis factor {alpha}, Interferon {gamma}, Mononuclear cells.


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