II: the effects of recombinant human insulin-like growth factor-1 on immunological recovery in the malnourished alcoholic rat.
OBJECTIVE
Immunological abnormalities are frequently observed in alcoholics with severe liver disease and are typically in association with immune abnormalities. Concomitantly, serum levels of insulin-like growth factor-1 (IGF-1) are frequently very low in these patients. Because IGF-1 is known to modulate both nutrition and immune status, the present study was undertaken to evaluate an in vivo rat model of alcoholism and malnutrition, the possibility of a therapeutic application for IGF-1.


METHODS
Controlled injury was induced by 14 days of calorie restriction and alcohol feeding that resulted in a 9% loss of body mass. Changes were compared with normal unrestricted control rats that gained 28% above their pretreatment body mass during the same period. Immunological impairment was assessed using thymus and spleen mass, cellularity and spleen T-lymphocyte function. Recovery was evaluated after 28 days of treatment using various combinations of: (1) high calorie intake, (2) cessation from alcohol feeding, and (3) IGF-1.


RESULTS
The thymus was most severely affected, losing 52.3% of its mass and 55.7% of its cellularity. The spleen was diminished, losing 31.2% of its mass and 41.9% of its cellularity. All of the spleen T-lymphocyte subsets were diminished, with CD5 affected the least (37.1 %) and CD8 affected the most severely (51.7%). During recovery, only the group treated with high calorie intake, no alcohol intake, and IGF-1 (group 8) had complete restoration of all immunological parameters, including a recovery of T-lymphocyte function. Continuous consumption of alcohol, even in the presence of high calories and IGF-1, produced an incomplete recovery.


CONCLUSIONS
Cessation of alcohol coupled with high calorie nutrition and IGF-1 treatment produced an accelerated improvement in host immunity. These animal studies suggest that IGF-1 is efficacious for this condition and supports the need for additional clinical studies.
Mendenhall
C L
CL
Department of Veterans Affairs Medical Center, and Department of Medicine, University of Cincinnati Medical Center, Ohio 45220, USA.
Roselle
G A
GA
Grossman
C J
CJ
Gartside
P
P
D000428:Alcohol Drinking; D000437:Alcoholism / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D002149:Energy Intake; D005247:Feeding Behavior; D007109:Immunity / Q000187:drug effects*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000627:therapeutic use; D009748:Nutrition Disorders / Q000188:drug therapy* / Q000276:immunology; D009752:Nutritional Status / Q000187:drug effects; D011502:Protein-Energy Malnutrition / Q000188:drug therapy / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology
D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I