Chronic alcohol accentuates simian acquired immunodeficiency syndrome-associated wasting.
BACKGROUND
Survival following human immunodeficiency virus (HIV) infection has improved significantly following the advent of highly active antiretroviral therapy. A large percentage of HIV-infected patients consume and abuse alcohol. Erosion of lean body mass is an important contributing factor to patient morbidity and mortality, and is a common feature of both chronic alcohol (ALC) consumption and acquired immunodeficiency syndrome (AIDS). We hypothesized that alcohol-induced loss in lean body mass is likely to exacerbate the AIDS wasting syndrome, particularly at the terminal stage of AIDS (SAIDS).


METHODS
This study examined the impact of chronic, intra-gastric ALC (5 h/d x 4 d/wk; blood alcohol levels = 55 mM to 60 mM) administration on body composition and muscle mass in simian immunodeficiency virus (SIV)-infected male Rhesus macaques in contrast to SIV-infected isocaloric (22 kcal/kg/d) sucrose (SUC)-infused control animals at the terminal stage of SIV infection.


RESULTS
At terminal stage, ALC/SIV+ animals had significantly lower body weight, body mass index, and limb muscle area than SUC/SIV+ animals. Both ALC/SIV+ and SUC/SIV+ animals had suppressed expression of insulin-like growth factor-I and increased expression of the ubiquitin ligase muscle-specific RING finger-1 mRNA. ALC increased mRNA expression of atrogin-1 (pre-SIV and at SAIDS) and tumor necrosis factor (TNF)-alpha (SAIDS). These changes were not associated with significant differences in fractional rates of muscle protein synthesis or in overall survival rate. These data show that chronic ALC exacerbated the loss of muscle mass at terminal SAIDS.


CONCLUSIONS
Our findings suggest the involvement of TNF-alpha and increased muscle proteolysis via atrogin-1 for the greater erosion of lean body mass at terminal SAIDS in ALC-treated Rhesus macaques.
Molina
Patricia E
PE
LSUHSC Department of Physiology and Alcohol Research Center, New Orleans, Louisiana 70112, USA. pmolin@lsuhsc.edu
Lang
Charles H
CH
McNurlan
Margaret
M
Bagby
Gregory J
GJ
Nelson
Steve
S
D000818:Animals; D000886:Anthropometry; D016516:CD4-CD8 Ratio; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000009:adverse effects*; D016207:Cytokines / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis; D018482:Muscle, Skeletal / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D019562:Viral Load; D019282:Wasting Syndrome / Q000209:etiology* / Q000276:immunology / Q000378:metabolism
D002492:Central Nervous System Depressants; D016207:Cytokines; D009124:Muscle Proteins; D000431:Ethanol; D007334:Insulin-Like Growth Factor I; D044767:Ubiquitin-Protein Ligases