Alcohol Ingestion by Donors Amplifies Experimental Airway Disease after Heterotopic Transplantation

Chronic Alcohol Ingestion and Predisposition to Lung “Cirrhosis”

“…This is reminiscent of prior work demonstrating enhanced airways disease in the setting of chronic alcohol ingestion in the heterotropic tracheal transplantation model, a model of chronic lung rejection also characterized by upregulation of TGFβ as well as intra-airway fibrosis (Mitchell and Guidot, 2007). However, the authors refrain from extrapolating their findings to humans with chronic fibrosing disorders, perhaps considering the lack of strong clinical and epidemiological data linking chronic alcohol ingestion with increased incidence of pulmonary fibrosis.…”

Alcohol Primes the Airway for Increased Interleukin‐13 Signaling

“…Overall, these studies suggest that clinically silent alcohol‐mediated lung dysfunction could promote tissue remodeling and fibrosis following injuries such as transplantation. In support of this contention, we recently demonstrated that chronic alcohol ingestion by donor rats amplifies airway fibrosis in recipients using the HTT model of airway fibrosis (Mitchell and Guidot, 2007). Associated with this alcohol‐mediated amplification in airway fibrosis was an increase in TGFβ 1 expression (Mitchell and Guidot, 2007).…”

“…In support of this contention, we recently demonstrated that chronic alcohol ingestion by donor rats amplifies airway fibrosis in recipients using the HTT model of airway fibrosis (Mitchell and Guidot, 2007). Associated with this alcohol‐mediated amplification in airway fibrosis was an increase in TGFβ 1 expression (Mitchell and Guidot, 2007). The mechanism by which prior alcohol ingestion by donor rats amplifies airway fibrosis in the transplanted airway is unclear; however, modulation of the IL‐13 signaling pathway represents a plausible pathway by which alcohol “primes” the airway for pro‐fibrotic signaling upon injury.…”

“…All procedures involving animals were performed with approval by the VA Medical Center Institutional Animal Care and Use Committee (IACUC), and in accordance with the NIH (Publication 85–23) Guide for the Care and use of Laboratory Animals, the Animal Welfare Act, and applicable VA Medical Center policies. Male Sprague–Dawley (SD; Charles River Laboratories, Wilmington, MA) rats (3 to 5 months of age) were fed the Lieber‐DeCarli isocaloric liquid diet (Research Diets, New Brunswick, NJ), containing either alcohol (36% total calories) or an isocaloric substitution with maltin–dextrin (control diet) for 8 weeks as described previously (Mitchell and Guidot, 2007). HTT was performed as described previously (Ramirez et al., 2004).…”

Update in Transplantation 2007

“…The authors found that experimental alcohol ingestion in donor animals led to greater allograft transforming growth factor (TGF)-b expression, myofibroblast transdifferentiation, and fibrosis when coupled with alloimmune inflammation (16). These findings should lead to further studies aimed at investigating evidence for this link in humans.…”