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ToxSci Advance Access originally published online on October 6, 2004
Toxicological Sciences 2004 82(2):656-660; doi:10.1093/toxsci/kfi002
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Toxicological Sciences vol. 82 no. 2 © Society of Toxicology 2004; all rights reserved.

IL-1 and TNF Antagonists Prevent Inhibition of Fracture Healing by Ethanol in Rats

Daniel S. Perrien*,{dagger},{ddagger}, Elizabeth C. Wahl*, William R. Hogue{ddagger},||, Ulrich Feige§, James Aronson*,||, Martin J. J. Ronis|||,||||, Thomas M. Badger|||| and Charles K. Lumpkin, Jr.*,1

* Laboratory for Limb Regeneration Research, Arkansas Children's Hospital Research Institute, Little Rock, Arkansas 722021; {dagger} Department of Physiology and Biophysics, {ddagger} The Center for Orthopaedic Research, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; § Department of Inflammation Research, Amgen, Inc., Thousand Oaks, California 91320; Department of Pediatrics, || Department of Orthopaedic Surgery, ||| Department of Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; and |||| Arkansas Children's Nutrition Center, Little Rock, Arkansas 72202

Received June 1, 2004; accepted September 22, 2004

We tested the hypothesis that combined administration of IL-1 and TNF antagonists would protect fracture healing from inhibition by chronic ethanol exposure. Adult male rats were fed a liquid diet ± ethanol (CON and ETOH) by intragastric infusion for three weeks prior to and three weeks after creation of an externally fixated tibial fracture. Beginning the day of fracture, one-half of each dietary group received 2.0 mg/kg/day IL-1ra and 2.0 mg/kg/2-days sTNFR1 (CON + ANTAG and ETOH + ANTAG), while all other animals received vehicle alone (CON + VEH and ETOH + VEH). Scoring of ex vivo radiographs and analysis by pQCT revealed a significantly lower incidence of bridging and reduced total mineral content in the ETOH + VEH group compared to all other groups. These results support, for the first time, the hypothesis that IL-1 and TNF antagonists are capable of protecting fracture healing from the inhibition associated with chronic ethanol consumption.

Key Words: alcohol; tumor necrosis factor; interleukin-1; interleukin-1 recombinant antagonist; repair; total enteral nutrition.


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J Bone Joint Surg BrHome page
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J Bone Joint Surg Br, December 1, 2007; 89-B(12): 1553 - 1560.
[Abstract] [Full Text] [PDF]



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