IL-1 and TNF antagonists prevent inhibition of fracture healing by ethanol in rats.
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.
Laboratory for Limb Regeneration Research, Arkansas Children's Hospital Research Institute, Little Rock, Arkansas 722021, USA.
Daniel S
DS
Perrien
Elizabeth C
EC
Wahl
William R
WR
Hogue
Ulrich
U
Feige
James
J
Aronson
Martin J J
MJ
Ronis
Thomas M
TM
Badger
Charles K
CK
Lumpkin
D000818:Animals; D002146:Bony Callus / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000633:toxicity*; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D017102:Fracture Healing / Q000187:drug effects*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008297:Male; D010012:Osteogenesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014057:Tomography, X-Ray Computed; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D015430:Weight Gain / Q000187:drug effects
D002492:Central Nervous System Depressants; D007375:Interleukin-1; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol