Changes in the IGF–IGFBP axis in critical illness

Abstract

In critical illness, serum concentrations of the growth hormone-dependent complexes containing insulin-like growth factors I and II are decreased. This is initially due to a transient growth hormone resistance, but in the longer term, the less pulsatile pattern of growth hormone secretion may be a major factor since only pulsatile growth hormone increases the levels of insulin-like growth factor-I and the acid-labile subunit. Other factors contributing to a low insulin-like growth factor level are nutritional deficiency and the direct effects of inflammatory cytokines. The growth hormone-independent proteins IGFBP-2, IGFBP-4 and IGFBP-6 increase in critical illness, suggesting a redistribution of insulin-like growth factors from growth hormone-dependent ternary complexes with IGFBP-3 and IGFBP-5 to binary complexes with these binding proteins, which might facilitate transport to the tissues. IGFBP-1, which is acutely regulated by metabolic status, is elevated on admission to intensive care but may fall in response to nutritional support. Initial evidence suggests that the level of IGFBP-1 may be predictive of outcome in critically ill patients, suggesting a possible prognostic role for this protein.