II : The effects of recombinant human insulin-like growth factor-1 on immunological recovery in the malnourished alcoholic rat

• Published in: Alcoholism, clinical and experimental research Vol. 21; no. 9; pp. 1682 - 1689
• Main Authors: MENDENHALL, C. L, ROSELLE, G. A, GROSSMAN, C. J, GARTSIDE, P
• Format: Journal Article
• Language: English
• Published: Baltimore, MD Lippincott Williams & Wilkins 01-12-1997
• Subjects: Alcohol Drinking; Alcoholism - drug therapy; Alcoholism - immunology; Alcoholism and acute alcohol poisoning; Animals; Biological and medical sciences; Body Weight; Disease Models, Animal; Energy Intake; Feeding Behavior; Immunity - drug effects; Insulin-Like Growth Factor I - pharmacology; Insulin-Like Growth Factor I - therapeutic use; Medical sciences; Nutrition Disorders - drug therapy; Nutrition Disorders - immunology; Nutritional Status - drug effects; Protein-Energy Malnutrition - drug therapy; Protein-Energy Malnutrition - immunology; Rats; Rats, Inbred Lew; Recombinant Proteins; Spleen - drug effects; Spleen - immunology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Thymus Gland - drug effects; Thymus Gland - immunology; Toxicology; Animal model; Immune response; Rat; Alcoholism; Rodentia; Nutrition disorder; Hepatic disease; Insulin like growth factor 1; Vertebrata; Chemotherapy; Mammalia; Treatment; Digestive diseases; Malnutrition; Nutritional status
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1097/00000374-199712000-00019

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.
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.
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.
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.