title: II: the effects of recombinant human insulin-like growth factor-1 on immunological recovery in the malnourished alcoholic rat.
abstract: 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.
authors.affiliation: Department of Veterans Affairs Medical Center, and Department of Medicine, University of Cincinnati Medical Center, Ohio 45220, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Mendenhall
authors.forename: G A
authors.initials: GA
authors.lastname: Roselle
authors.forename: C J
authors.initials: CJ
authors.lastname: Grossman
authors.forename: P
authors.initials: P
authors.lastname: Gartside
mesh_terms: 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
chemical_list: D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I