The insulin-like growth factor system in critical illness: pathophysiology and therapeutic potential.
Insulin-like growth factor-I (IGF-I) mediates at least some of the anabolic actions of growth hormone (GH). Most IGF-I in the circulation is held in a 150 kD complex with IGF binding protein-3 (IGFBP-3). In critical illness there is GH resistance which results in low serum levels of IGF-I, although its bioavailability may initially be maintained by serum proteases which modify the IGFBP-3 and reduce its affinity for IGF-I. Attempts to treat the protein catabolism associated with critical illness by hyperalimentation have had only limited success. The use of recombinant human GH combined with nutritional support increases protein synthesis, but the GH resistance necessitates high doses and GH has adverse direct metabolic effects including insulin resistance and impaired glucose tolerance. Treatment with recombinant human IGF-I inhibits proteolysis but may cause hypoglycaemia if administered intravenously. Its effects are often transient and show tachyphylaxis. A combination of GH and IGF-I with nutritional support may be the most effective treatment to counter the catabolism associated with critical illness. The costs of such therapy could be offset by shorter hospital stays. Further controlled studies are necessary to establish the clinical effectiveness of growth factor treatment.
Crown
A L
AL
Department of Medicine, University of Bristol, Bristol Royal Infirmary, Marlborough Street, Bristol BS28HW, UK.
Holly
J M
JM