WASTING IN THE ACQUIRED-IMMUNE-DEFICIENCY-SYNDROME IS ASSOCIATED WITHMULTIPLE DEFECTS IN THE SERUM INSULIN-LIKE GROWTH-FACTOR SYSTEM

OBJECTIVE The aim of this investigation was to characterize the GH-IGF axis of patients with AIDS associated wasting. A special emphasis was placed on determining whether IGF binding proteins (IGFBPs) of patien ts who have lost more than 10% of their ideal body mass are structural ly different from the IGFBPs of patients with no weightless. DESIGN AN D PATIENTS A cross-sectional study of 11 AIDS patients was performed t o determine whether the IGF system is abnormal in AIDS patients with w asting. Seven additional AIDS patients were followed longitudinally to determine whether AIDS patients experience longterm changes to their IGF system. MEASUREMENTS Serum levels of GH and IGF-I were measured by radioimmunoassay, IGF-II was measured by radioreceptor assay, and IGF BP-1 was measured by an enzyme linked immunoassay. IGFBP-3 and IGFBP-3 protease activity were measured by ligand blotting and a BP-3 proteas e assay, respectively, IGFBP-3 ternary complex formation and IGFBP-1 p hosphovariants were analysed by non-denaturing PAGE.RESULTS AIDS patie nts who had lost more than 10% of their ideal body mass demonstrated a 55% reduction in serum IGF-I (81 vs 179 mu g/l) and a 70% reduction i n IGF-II (226 vs 776 mu g/l), compared to healthy HIV negative subject s. IGF-I levels were depressed, in some patients, despite high serum l evels of GH. AIDS patients who had lost more than 10% of their ideal b ody mass had low levels of IGFBP-3 and a reduced ability to form the I GFBP-3 ternary complex. The IGFBP-3 ternary complex could be restored only upon addition of pure IGFBP-3 and acid labile subunit to serum, S erum IGFBP-1 was increased more than threefold compared to control sub jects (90 vs 24 mu g/l). IGFBP-1 was present as a free phosphoprotein in AIDS patients with low levels of IGF-I and in a bound form when ser um IGF-I levels were normal. Changes in the GH-IGF axis were sustained for up to 25 months in AIDS patients with wasting. CONCLUSIONS AIDS w asting is associated with a GH resistant state that results in low lev els of serum IGF-I, IGF-II and IGFBP-3, elevated levels of phosphoryla ted IGFBP-1, and a reduced ability to form the IGFBP-3 ternary complex .