ALCOHOL: IMMUNOMODULATION AND DISEASE PATHOGENESIS

The overall goals of this proposal are to develop a center which
will foster research concerning the role of ethanol on: (1)
cellular immune function in animal models, (2) immunosuppression
and development of acquired immunodeficiency diseases including
retrovirus infection, and (3) mechanisms of liver toxicity via
immunomodulation. Our approaches involve a multidisciplinary, basic science-oriented,
research effort. It will develop an alcohol research center and
include: 1) The relationships of alcohol use, retrovirus infection,
immunomodulation and AIDS development to:
- determine alcohol's effects on death rates
- investigate in depth alcohol's actions on immune functions in
mice with various levels of alcohol intake.
-measure the effects of cessation of high alcohol use on cellular
immune function
-study in detail the immunological changes due to alcohol as a
cofactor during retroviral infection on resistance to other
pathogens
-determine ways to stimulate ethanol-suppressed host defense and
disease resistance during retroviral infection. 2) The use of well-defined animal model systems to:
- determine interactions between alcohol use, nutritional stresses,
immuno-architecture changes and the resulting changes in resistance
to murine retorvirus.
- investigate the long-term effects of alcohol to modulate cellular
immune functions as they correlate with enhancement of chemically-
induced liver cancer in rats.
-determine the role of toxin and alcohol-altered Kupffer cell
functions in liver damage in rats.
- study alcohol's effects on sinusoidal permeability, tissue
oxygenation, cell migration in lymph.
-measure and study host defense function of macrophages and Kupffer
cells in vivo including in vivo microscopy as modified by ethanol
and retroviral disease.