Interleukin 1 receptor antagonist inhibits localized bone formation in vivo.
OBJECTIVE
To test the in vivo effects of interleukin 1 receptor antagonist (IL-1ra) on bone formation and tissue ingrowth using an implantable bone ingrowth chamber that can be infused with test solutions.


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.


CONCLUSIONS
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.
Ma
Ting
T
Department of Orthopaedic Surgery, Stanford University School of Medicine, Medical Center, 300 Pasteur Drive, Stanford, CA 94305-5341, USA.
Miyanishi
Keita
K
Trindade
Michael C D
MC
Genovese
Mark
M
Regula
Donald
D
Smith
R Lane
RL
Goodman
Stuart B
SB
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D007124:Immunoenzyme Techniques; D007260:Infusion Pumps; D053590:Interleukin 1 Receptor Antagonist Protein; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects*; D011817:Rabbits; D017472:Receptors, Interleukin-1 / Q000819:agonists*; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology*; D000071681:Tartrate-Resistant Acid Phosphatase; D013977:Tibia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D053590:Interleukin 1 Receptor Antagonist Protein; D007527:Isoenzymes; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase