Submitted to: Toxicological Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/22/2004
Publication Date: 10/6/2004
Citation: Perrien, D.S., Wahl, E.C., Hogue, W.R., Feige, U., Aronson, J., Ronis, M.J., Badger, T.M., Lumpkin, C.K. 2004. Il-1 and tnf antagonists prevent inhibition of fracture healing by ethanol in rats. Toxicological Sciences. 82(2):656-660. Interpretive Summary: Alcohol constitutes a significant portion of the total caloric intake of Americans and we have been interested in the beneficial and adverse effects of alcohol intake in the context of an otherwise nutritionally complete diet. Distraction osteogenesis is a clinically employed procedure to lengthen and straighten bone of children born with born deformities. During this process, a bone is fractured and slowly pulled apart. New bone formed in the gap between the edges of the fracture and this provided a model for studying form formation. The bone actually can be formed at a rate greater than occurs in fetal development, thus this is an excellent model for bone formation during development. We tested the effects of an alcohol-containing diet in rats undergoing distraction osteogenesis and found that alcohol inhibited new bone formation and endogenous compound, IL-1 and a new drug, TNF Anatgonists, block the inhibition of alcohol on born formation. These results suggest that IL-1 and TNF are important components of bone formation during development and this model provide a means to study dietary factors on bone development in the future.
Technical Abstract: 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.