II - THE EFFECTS OF RECOMBINANT HUMAN INSULIN-LIKE GROWTH-FACTOR-I ONIMMUNOLOGICAL RECOVERY IN THE MALNOURISHED ALCOHOLIC RAT

Background/aims: Immunological abnormalities are frequently observed i n alcoholics with severe liver disease and are typically in associatio n with immune abnormalities. Concomitantly, serum revels of insulin-li ke growth factor-1 (IGF-1) are frequently very low in these patients, Because IGF-1 is known to modulate both nutrition and immune status, t he present study was undertaken to evaluate an in vivo rat model of al coholism and malnutrition, the possibility of a therapeutic applicatio n for IGF-1. Methods: Controlled injury was induced by 14 days of calo rie restriction and alcohol feeding that resulted in a 9% loss of body mass. Changes were compared with normal unrestricted control rats tha t gained 28% above their pretreat ment body mass during the same perio d, 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 combination of: (1) high calo rie 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 i ts mass and 41.9% of its cellularity. All of the spleen T-lymphocyte s ubsets were diminished, with CD5 affected the least (37.1%) and CD8 af fected the most severely (51.7%). During recovery, only the group trea ted with high calorie intake, no alcohol intake, and IGF-1 (group 8) h ad complete restoration of all immunological parameters, including a r ecovery of T-lymphocyte function, Continuous consumption of alcohol, e ven in the presence of high calories and IGF-1, produced an incomplete recovery. Conclusion: Cessation of alcohol coupled with high calorie nutrition and IGF-1 treatment produced an accelerated improvement in h ost immunity, these animal studies suggest that IGF-1 is efficacious f or this condition and supports the need additional clinical studies.