Ligand-binding activity and immunoreactivity of insulin-like growth factor binding proteins in patients with colorectal carcinoma and postoperative sepsis

Abstract

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 non-surviving 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 revea 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, ligand-reactivity 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’ metabolic potential to combat a disease.

Keywords

• colorectal carcinoma
• igfbps
• sepsis
• survival