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Interleukin 1 Receptor Antagonist Inhibits Localized Bone Formation in Vivo
TING MA, KEITA MIYANISHI, MICHAEL C.D. TRINDADE, MARK GENOVESE, DONALD REGULA, R. LANE SMITH, and STUART B. GOODMAN
ABSTRACT.
Methods. The bone ingrowth chamber was implanted in the proximal tibia of 10 mature NZW rabbits unilaterally. After an initial osseointegration period, the chambers were emptied of tissue and infused with either 0.05% bovine serum albumin (BSA) in phosphate buffered saline (PBS) or an IL-1ra solution for 4-week periods, which were separated by 4-week periods of no infusion. Tissue samples harvested from each chamber were snap-frozen and examined by histology and immunohistochemistry. Results. The chambers were filled with longitudinally-oriented woven bone in a fibrovascular stroma during periods of infusion of 0.05% BSA in PBS or during periods without infusion. In contrast, infusion of IL-1ra for 4 weeks prevented tissue ingrowth in 4 of 6 chambers, and in 2 chambers exhibiting tissue ingrowth, bone formation was decreased. Bone formation remained at a lower level during the subsequent two 4-week periods without infusion after IL-1ra was discontinued, compared to samples prior to the IL-1ra treatment. Conclusion. The results showed that tissue ingrowth and bone formation were suppressed in an in vivo model by continuous infusion of IL-1ra at an early phase of tissue regeneration and differentiation. (J Rheumatol 2003;30:2547-52) Key Indexing Terms:
INTERLEUKIN 1 RECEPTOR ANTAGONIST
From the Department of Orthopaedic Surgery, Division of Immunology and Rheumatology, and Department of Pathology, Stanford University School of Medicine, Stanford, California, USA. Supported in part by Zimmer Inc., Amgen Inc., and Durect Corporation. T. Ma, MD, Research Assistant; K. Miyanishi, MD, PhD, Postdoctoral Fellow; M.C.D. Trindade, MS, Research Assistant; R.L. Smith, PhD, Professor; S.B. Goodman, MD, PhD, Professor, Department of Orthopaedic Surgery; M. Genovese, MD, Assistant Professor, Division of Immunology and Rheumatology; D. Regula, MD, Associate Professor, Department of Pathology. Address reprint requests to Dr. S.B. Goodman, Department of Orthopedic Surgery, Stanford University Medical Center, 300 Pasteur Drive, R144, Stanford, CA 94305-5341. E-mail: goodbone@stanford.edu Submitted January 27, 2003; revision accepted April 23, 2002. |