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Scientific Articles   |    
Binge Alcohol Exposure Modulates Rodent Expression of Biomarkers of the Immunoinflammatory Response to Orthopaedic Trauma
Benjamin W. Sears, MD1; Dustin Volkmer, MD1; Sherri Yong, MD1; Ryan D. Himes, BS1; Kristen Lauing, BS1; Michelle Morgan, BS1; Michael D. Stover, MD1; John J. Callaci, PhD1
1 Department of Orthopaedic Surgery and Rehabilitation (B.W.S., D.V., R.D.H., K.L., M.M., M.D.S., and J.J.C.) and Department of Pathology (S.Y.), Loyola University Medical Center, 2160 South 1st Avenue, Maywood, IL 60153. E-mail address for B.W. Sears: bwsears@gmail.com. E-mail address for D. Volkmer: dvolkmer@lumc.edu. E-mail address for S. Yong: syong@lumc.edu. E-mail address for R.D. Himes: rhimes@lumc.edu. E-mail address for K. Lauing: klauing@lumc.edu. E-mail address for M. Morgan: mimorgan@lumc.edu. E-mail address for M.D. Stover: mstover@lumc.edu. E-mail address for J.J. Callaci: jcallaci@lumc.edu
View Disclosures and Other Information
Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants of less than $10,000 from the National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism (grant R01 AA016138). Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity.

Investigation performed at Loyola University Medical Center, Maywood, Illinois

Copyright © 2011 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2011 Apr 20;93(8):739-749. doi: 10.2106/JBJS.J.00318
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Abstract

Background: 

Alcohol is a known modulator of the immune system and host-defense response. Alcohol abuse is common in trauma patients, although the influence of alcohol intoxication on the inflammatory response following major orthopaedic injury remains unknown. The aim of this investigation was to examine the influence of binge alcohol exposure on biomarkers of the systemic inflammatory response following bilateral traumatic femoral fracture in a rodent model.

Methods: 

Ninety-two Sprague-Dawley rats were administered intraperitoneal injections of either saline solution or alcohol for three days. These animals then underwent a sham procedure or bilateral femoral intramedullary pinning and mid-diaphyseal closed fracture via blunt guillotine. The animals were killed at specific time points after the injury. Serum and lung tissue were collected, and twenty-five inflammatory markers were analyzed by immunoassay. Histological sections of lung tissue were evaluated by a board-certified pathologist.

Results: 

Bilateral femoral fracture significantly (p < 0.05) increased multiple serum biomarkers of inflammation. Binge alcohol treatment prior to injury significantly suppressed the increase in serum levels of interleukin (IL)-6, white blood cells, IL-2, IL-10, and C-reactive protein after the fracture. However, alcohol-treated animals were found to have increased pulmonary levels of IL-6, IL-1ß, IL-2, and macrophage inflammatory protein-1a following bilateral femoral fracture. In addition, lung tissue harvested following alcohol treatment and injury demonstrated increased pathologic changes, including parenchymal, alveolar, and peribronchial leukocyte infiltration and significantly elevated pulmonary wet-to-dry ratio, indicative of pulmonary edema.

Conclusions: 

Our results indicate that acute alcohol intake prior to bilateral femoral fracture with fixation in rats modulates the inflammatory response after injury in a tissue-dependent manner. Although serum biomarkers of inflammation were suppressed in alcohol-treated animals following injury, several measures of pulmonary inflammation including cytokine levels, histological changes, and findings of pulmonary edema were significantly increased following fracture with the presence of alcohol.

Clinical Relevance: 

These findings indicate that alcohol modulates the inflammatory response after a major orthopaedic injury and that analysis of serum markers of inflammation after trauma may not represent the pulmonary inflammatory status in acutely intoxicated patients.

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    References

    Accreditation Statement
    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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