EFFECTS OF RECOMBINANT HUMAN INSULIN-LIKE GROWTH-FACTOR-I AND RECOMBINANT HUMAN GROWTH-HORMONE ON ANABOLISM AND IMMUNITY IN CALORIE-RESTRICTED ALCOHOLIC RATS

Patients with severe alcoholic liver injury exhibit very low serum ins ulin-like growth factor-1 (IGF-1) concentrations, along with many of t he symptoms that might occur with an IGF-1 deficiency state (including severe protein calorie malnutrition and immunosuppression). This stud y was performed to assess the effects of recombinant human (rh) IGF-1 and/or rh growth hormone (rhGH) on anabolism and immunity in the calor ie-restricted, immunosuppressed alcoholic rat. Methods: Undernutrition was induced by calorie restriction such that each animal consumed 40% of ad libitum-fed controls. Alcohol was administered orally in the di et such that the mean dairy intake was 9.4 g/kg/day. rhIGF-1 was admin istered by continuous subcutaneous infusion (380 mu g/day) using a 14- day miniosmotic pump; rhGH was given by subcutaneous injections (400 m u g/day). Matching placebo groups were also studied. Results: On this regimen, ad libitum-fed controls were well nourished and increased bod y weight 34%, whereas Restricted controls lost 7.7% and Restricted alc ohol-fed rats lost 15.2%. Significant but incomplete reversal of under nutrition was achieved with hormone therapy. Best improvement was obta ined with combined therapy: rhIGF-1 + rhGH (p < 0.005; placebo versus active treatments). Immunologic impairment was observed to be severe i n both thymus and spleen. The most severe changes were seen in thymi o f the calorie-restricted, alcohol-fed rats, wherein 98% of the T lymph ocytes were test rhIGF-1 treatment, but not rhGH, produced significant improvements in thymus. This was most pronounced in control rats (p < 0.005). Splenic T lymphocytes were less impaired and were more respon sive to rhIGF-1 treatment; there was a maximum loss of 71% of T cells in Restricted, alcohol-fed rats. rhIGF-1 treatment completely restored splenic cellularity, as well as each of the T lymphocytes studied: CD 5, CD4, and CD8. Functional status of splenic T lymphocytes was assess ed by blast transformation after concanavalin A stimulation. Calorie r estriction did not impair significantly this function in controls [Lie ber-DeCarli control diet (LCD)]. However, it was significantly impaire d in the Restricted, alcohol-fed rats (p = 0.003). In the presence of continued calorie restriction and alcohol, this function was not resto red with either hormone (rhIGF-1 and/or rhGH). Their role in facilitat ing functional recovery after calories is restored, and alcohol is dis continued is under investigation.