A large proportion of the cases of pancreatitis in human beings are associated with alcohol consumption, but pancreatitis develops in only a minority of people who abuse alcohol. These observations support the argument that factors other than alcohol or alcohol metabolisms are involved in the development of alcoholic pancreatitis. The hypothesis that will be investigated by the research proposed in this exploratory/developmental grant application is that one co-factor for the development of acute and chronic alcoholic pancreatitis is an infection with a virus that has a tropism for the pancreas. This viral infection is hypothesized to initiate the damage in the pancreas and this damage is more severe in individuals who abuse alcohol through an alcohol-associated sensitization of the pancreas. A murine model of alcohol consumption that is done with the use of C57BL/6 and Balb/c mice provided ethanol (ETOH) in either a liquid diet or in the drinking water will be used for these studies. Specifically, mice provided ETOH and control mice (i.e., pair-fed and chow-fed) will be infected with coxsackievirus group B, stereotype 3 (CVB3) and pancreas damage and fibrosis will be evaluated. The hypotheses will be addressed by three specific aims: 1) To develop the model system to characterize the effects of ETOH and CVB3 infection of the pancreas; 2) To determine the effect of ETOH consumption on production of pro-inflammatory cytokines during the viral infection; 3) To determine the effects of chronic ETOH consumption, with an ETOH-in-drinking-water model system, on pathologic effects in the pancreas after viral infection. The development and characterization of this model system will provide a useful model of alcoholic pancreatitis that will allow follow-up studies to investigate mechanisms of ETOH to sensitize the pancreas to damage. The model system will also allow critical studies of possible therapeutic interventions.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
Special Emphasis Panel (ZAA1-DD (10))
Program Officer
Purohit, Vishnu
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Nebraska Medical Center
Schools of Medicine
United States
Zip Code
Cook, Robert T; Schlueter, Annette J; Coleman, Ruth A et al. (2007) Thymocytes, pre-B cells, and organ changes in a mouse model of chronic ethanol ingestion--absence of subset-specific glucocorticoid-induced immune cell loss. Alcohol Clin Exp Res 31:1746-58
Jerrells, Thomas R; Vidlak, Debbie; Strachota, Jennifer M (2007) Alcoholic pancreatitis: mechanisms of viral infections as cofactors in the development of acute and chronic pancreatitis and fibrosis. J Leukoc Biol 81:430-9
Kovacs, Elizabeth J; Jerrells, Thomas R; Alcohol and Immunology Research Interest Group (2004) Alcohol and immunology: introduction to and summary of the 2003 Alcohol and Immunology Research Interest Group (AIRIG) meeting. Alcohol 33:171-4
Clemens, Dahn L; Jerrells, Thomas R (2004) Ethanol consumption potentiates viral pancreatitis and may inhibit pancreas regeneration: preliminary findings. Alcohol 33:183-9