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.
Perrien
Daniel S
DS
Laboratory for Limb Regeneration Research, Arkansas Children's Hospital Research Institute, Little Rock, Arkansas 722021, USA.
Wahl
Elizabeth C
EC
Hogue
William R
WR
Feige
Ulrich
U
Aronson
James
J
Ronis
Martin J J
MJ
Badger
Thomas M
TM
Lumpkin
Charles K
CK
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