Effects of acute ethanol exposure on the early inflammatory response after excisional injury.
BACKGROUND
Alcohol consumption is involved in over half of all trauma-related injuries. These patients are known to exhibit a higher incidence of mortality and morbidity following injury compared with patients not exposed to ethanol. As studies from our laboratory demonstrated that ethanol exposure impairs re-epithelialization and angiogenesis after dermal wounding and because the earlier inflammatory phase of wound healing is likely to influence later responses, we chose to examine neutrophil infiltration and chemokine and proinflammatory cytokine levels in the skin following administration of a dermal excisional wound.


METHODS
BALB/c mice were given ethanol at a dose designed to increase blood alcohol concentration to 100 to 120 mg/dL at 30 minutes after treatment. Mice were then subjected to a full-thickness excisional wound. Wounds from ethanol and saline-treated mice were collected within the first 24 hours postinjury to assess neutrophil infiltration and myeloperoxidase (MPO) activity, neutrophil chemoattractant macrophage inflammatory protein-2 (MIP-2) and KC levels, and proinflammatory cytokine interleukin-1 beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) levels.


RESULTS
At 12 and 24 hours after injury, MPO in wounds from ethanol-exposed mice was significantly reduced compared with wounds from vehicle-treated animals. Despite this, histological examination of wounds did not reveal a difference in neutrophil infiltration between the 2 groups. Peak levels of MIP-2 and KC observed at 12 hours postinjury were decreased in wounds from ethanol-treated mice by 32 and 45%, respectively, relative to wounds from control mice. Levels of TNFalpha and IL-1beta (potent inducers of MIP-2 and KC, as well as neutrophil activation) were also assessed. Levels of TNFalpha were not elevated in either group after injury. However, IL-1beta demonstrated significantly lower peak levels at 6 hours postinjury in wounds from ethanol-treated mice, 58% less than wounds from controls.


CONCLUSIONS
These studies reveal that early dermal inflammatory responses including MPO activity, production of MIP-2, KC, and IL-1beta are impaired in mice given ethanol before injury, which may also have detrimental affects on later stages of wound healing.
Fitzgerald
Daniel J
DJ
Department of Cell Biology, Neurobiology and Anatomy, Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, Illinois 60153, USA.
Radek
Katherine A
KA
Chaar
Mitchell
M
Faunce
Douglas E
DE
DiPietro
Luisa A
LA
Kovacs
Elizabeth J
EJ
D000818:Animals; D002492:Central Nervous System Depressants / Q000633:toxicity*; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D002492:Central Nervous System Depressants; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D053583:Interleukin-1beta; D000431:Ethanol; D009195:Peroxidase