CHANGES IN PROTEIN-TURNOVER, IGF-I AND IGF BINDING-PROTEINS IN CHILDREN WITH CANCER

Changes in insulin-like growth factor-I (IGF-I) and insulin-like growt h factor binding proteins (IGEBPs) were correlated with protein synthe sis and breakdown using [1-C-13]leucine before chemotherapy and during subsequent febrile neutropenia (FN) in eight children with cancer, ag ed 6.3-17.5 y. IGF-I levels were similar to age-matched controls befor e chemotherapy (mean +/- SEM: 250 +/- 28 and 228 +/- 22 mu g l(-1), re spectively). During FN, IGF-I fell to 156 +/- 22 mu g l(-1) (p = 0.02) , and rose to 276 +/- 27 mu g l(-1) with recovery at 6 months (p = 0.0 04). Similarly, IGFBP-3 decreased from 4.0 +/- 0.2 mg l(-1) before che motherapy to 3.0 +/- 0.3 mg l(-1) during FN (p = 0.01), and returned t o 4.1 +/- 0.2 mg l(-1) at 6 months (p = 0.01). IGF-I correlated with I GFBP-3 (r = +0.7, p < 0.001). Scanning densitometry showed a decrease in IGFBP-3 from 94 to 54% during FN, when the presence of IGFBP-3 prot ease activity was observed. Compared with normal human serum, IGFBP-2 was elevated throughout the study. IGFBP-1 increased from 14.6 +/- 3.5 to 30.6 +/- 2.8 mu g l(-1) (p = 0.004), whereas serum insulin decreas ed from 26.5 +/- 6.8 to 7.8 +/- 0.8 mU l(-1) (p = 0.03) before and dur ing FN, respectively. Whilst IGF-I and IGFBP-3 fell, daytime growth ho rmone increased from 3.3 +/- 0.6 to 6.7 +/- 0.8 mU l(-1) (p = 0.01), a nd cortisol from 197 +/- 48 to 594 +/- 98 nmol l(-1) (p = 0.005). Albu min decreased from 47 +/- 2 to 38 +/- 2 g l(-1) (p = 0.004) and improv ed to 47 +/- 2 g l(-1) with recovery (p = 0.003). Protein synthesis in creased from 4.5 +/- 0.4 to 5.0 +/- 0.6 g kg(-1) d(-1) before chemothe rapy and during FN, while protein breakdown rose from 5.4 +/- 0.4 to 6 .3 +/- 0.4 kg(-1) d(-1). Increasing protein breakdown was related to f alling IGF-I and IGFBP-3 levels. Modification of IGFBP-3 by circulatin g proteolytic activity may alter IGF bioavailability, allowing protein synthesis to increase during periods of severe catabolic stress.