Ligand-Binding Activity and Immunoreactivity of Insulin-Like growth Factor Binding Proteins in Patients with Colorectal Carcinoma And Postoperative Sepsis

Abstract

Summary Background: Postoperative sepsis alters the growth hormone (GH)/insulin-like growth factor (IGF) axis leading to reduction in IGF-I and IGF-binding protein (IGFBP) 3 and elevation of GH-independent IGFBPs. The aim of this work was to investigate the differences in ligand binding and immunoreactivity of the circulating IGFBPs between surviving and nonsurviving septic patients that underwent colorectal surgery. Methods: Ligand binding was detected only for IGFBP-3 and IGFBP-2 and, consecutively, immunoreactivity was assayed for these IGFBPs. Results: In survivors both ligand- and immunoblotting re - vea led two IGFBP-3 isoforms (40 and 45 kDa). In non-survivors ligand-blotting hardly detected the IGFBP-3 doublet, intact immunoreactive IGFBP-3 was not detected and the major species was the 29 kDa fragment. Immunoblotting with an anti-IGFBP-2 antibody indicated an increase in the amount of intact and fragmented IGFBP-2 along the progression of illness in the non-survivors. The amount of intact IGFBP-2 in the survivors did not differ during the treatment. The amount of immunoreactive IGFBP-2 corresponded to its ligand-binding activity. Conclusions: According to the results reported here, ligandreactivity and immunoreactivity of IGFBP-3 should be taken into account as variables that affect the GH/IGF axis in critically ill patients. The degree of their variation is not directly correlated to the total amount of IGFBP-3 determined by the immunoassay, but they may be related to patients’ meta bolic potential to combat a disease.