Thymocytes, Pre-B Cells, and Organ Changes in a Mouse Model of Chronic Ethanol Ingestion—Absence of Subset-Specific Glucocorticoid-Induced Immune Cell Loss

Authors

  • Robert T. Cook,

    1. From the Departments of Pathology (RTC, AJS, RAC, LT, MBN, THH, TJW) and Internal Medicine (ZKB, NBR), University of Iowa Carver College of Medicine, and the Veterans Affairs Medical Center, Iowa City, Iowa 52242; and the Department of Pathology and Microbiology (TRJ), University of Nebraska Medical Center, Omaha, Nebraska 68198.
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  • Annette J. Schlueter,

    1. From the Departments of Pathology (RTC, AJS, RAC, LT, MBN, THH, TJW) and Internal Medicine (ZKB, NBR), University of Iowa Carver College of Medicine, and the Veterans Affairs Medical Center, Iowa City, Iowa 52242; and the Department of Pathology and Microbiology (TRJ), University of Nebraska Medical Center, Omaha, Nebraska 68198.
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  • Ruth A. Coleman,

    1. From the Departments of Pathology (RTC, AJS, RAC, LT, MBN, THH, TJW) and Internal Medicine (ZKB, NBR), University of Iowa Carver College of Medicine, and the Veterans Affairs Medical Center, Iowa City, Iowa 52242; and the Department of Pathology and Microbiology (TRJ), University of Nebraska Medical Center, Omaha, Nebraska 68198.
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  • Lorraine Tygrett,

    1. From the Departments of Pathology (RTC, AJS, RAC, LT, MBN, THH, TJW) and Internal Medicine (ZKB, NBR), University of Iowa Carver College of Medicine, and the Veterans Affairs Medical Center, Iowa City, Iowa 52242; and the Department of Pathology and Microbiology (TRJ), University of Nebraska Medical Center, Omaha, Nebraska 68198.
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  • Zuhair K. Ballas,

    1. From the Departments of Pathology (RTC, AJS, RAC, LT, MBN, THH, TJW) and Internal Medicine (ZKB, NBR), University of Iowa Carver College of Medicine, and the Veterans Affairs Medical Center, Iowa City, Iowa 52242; and the Department of Pathology and Microbiology (TRJ), University of Nebraska Medical Center, Omaha, Nebraska 68198.
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  • Thomas R. Jerrells,

    1. From the Departments of Pathology (RTC, AJS, RAC, LT, MBN, THH, TJW) and Internal Medicine (ZKB, NBR), University of Iowa Carver College of Medicine, and the Veterans Affairs Medical Center, Iowa City, Iowa 52242; and the Department of Pathology and Microbiology (TRJ), University of Nebraska Medical Center, Omaha, Nebraska 68198.
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  • Marcus B. Nashelsky,

    1. From the Departments of Pathology (RTC, AJS, RAC, LT, MBN, THH, TJW) and Internal Medicine (ZKB, NBR), University of Iowa Carver College of Medicine, and the Veterans Affairs Medical Center, Iowa City, Iowa 52242; and the Department of Pathology and Microbiology (TRJ), University of Nebraska Medical Center, Omaha, Nebraska 68198.
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  • Nancy B. Ray,

    1. From the Departments of Pathology (RTC, AJS, RAC, LT, MBN, THH, TJW) and Internal Medicine (ZKB, NBR), University of Iowa Carver College of Medicine, and the Veterans Affairs Medical Center, Iowa City, Iowa 52242; and the Department of Pathology and Microbiology (TRJ), University of Nebraska Medical Center, Omaha, Nebraska 68198.
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  • Thomas H. Haugen,

    1. From the Departments of Pathology (RTC, AJS, RAC, LT, MBN, THH, TJW) and Internal Medicine (ZKB, NBR), University of Iowa Carver College of Medicine, and the Veterans Affairs Medical Center, Iowa City, Iowa 52242; and the Department of Pathology and Microbiology (TRJ), University of Nebraska Medical Center, Omaha, Nebraska 68198.
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  • Thomas J. Waldschmidt

    1. From the Departments of Pathology (RTC, AJS, RAC, LT, MBN, THH, TJW) and Internal Medicine (ZKB, NBR), University of Iowa Carver College of Medicine, and the Veterans Affairs Medical Center, Iowa City, Iowa 52242; and the Department of Pathology and Microbiology (TRJ), University of Nebraska Medical Center, Omaha, Nebraska 68198.
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  • This work was supported by NIH AA-09598, AA-014405 (RTC), AA-014400 (TJW), AA-014406 (AJS), AA-014418 (ZKB), AA-012450, AA-013841 (TRJ) and AA-013275 (NBR), The Department of Pathology and the University of Iowa Carver College of Medicine, and the Department of Pathology and Microbiology of the University of Nebraska Medical Center.

Reprint requests: Robert T. Cook, MD, PhD, Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242; Fax: 319-335-8453; E-mail: robert-cook@uiowa.edu

Abstract

Background:  The well-known immune deficiency of the chronic alcoholic dictates the need for a long-term rodent ethanol administration model to evaluate the baseline immunologic effects of chronic ethanol abuse, and investigate the genetic determinants of those effects. Much published work with rodents has shown clearly that acute ethanol administration and short-term ethanol-containing liquid diets both cause elevated corticosterone and can cause significant thymocyte, pre-B cell and peripheral lymphocyte losses. Such losses may mask more subtle alterations in immune homeostasis, and in any case are generally short-lived compared with the span of chronic ethanol abuse. Thus, it is important to have a model in which long-term immune alterations can be studied free of corticosteroid-induced cell losses.

Methods:  We have utilized chronic 20% (w/v) ethanol in water administration to several mouse strains for prolonged periods of time and evaluated serum corticosterone, immunologic stress parameters, and other organ changes by standard methods.

Results:  We now confirm earlier reports that chronic ethanol in water administration to mice does not produce net elevations of corticosterone, although diurnal variation is altered. Importantly, there is neither selective loss of immune cell populations known to be corticosteroid sensitive, CD4+CD8+ thymocytes and pre-B cells, nor are changes observed in the histologic appearance of the thymus. Nonetheless, there are significant chronic ethanol effects in other tissues, including reduced heart weight, mild hepatic steatosis, alterations of gut flora, increased serum peptidoglycan, and as published elsewhere, immune system abnormalities.

Conclusions:  This model of ethanol administration is convenient, sustainable for up to 1 year, demonstrably feasible in several mouse strains, permits good weight gains in most strains, and results in significant changes in a number of organs. The administration method also will permit modeling of long-term steady abuse punctuated by major binges, and is suitable for supplementation studies using water soluble additives. Overall, the method is useful for a wide range of studies requiring a chronic low-stress method of ethanol administration.

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