Exacerbated inflammatory response induced by insulin-like growth factor I treatment in rats with ischemic acute renal failure

In agreement with recent studies showing a deleterious effect of growth hor mone treatment in critically ill patients, preliminary data showed that ins ulin-like growth factor I (IGF-I) administration increased the mortality ra te of rats with ischemic acute renal failure (ARF). The present study was d esigned to investigate the mechanism responsible for this unexpected effect . Male rats with ischemic ARF were given subcutaneous IGF-I, 50 mug/100 g a t 0, 8, and 16 h after reperfusion (ARF+IGF-I, n=5) or were untreated (ARF, n=5). A group of 5 sham-operated rats were used as controls. Rats were kil led 48 h after declamping, and the following studies were performed: in ser um, creatinine and urea nitrogen; and in kidneys, histologic damage score, cellular proliferation by bromodeoxyuridine labeling, apoptosis by morpholo gic criteria, macrophage infiltration by immunohistochemistry using a speci fic antibody against ED-1, neutrophil infiltration by naphthol AS-D chloroa cetate esterase staining, and levels of IGF-I and IGF-I receptor mRNA by RN ase protection assay. ARF and ARF+IGF-I groups had a severe and similar deg ree of renal failure. Kidney damage was histologically more evident in ARFIGF-I (1.9 +/-0.1) than in ARF (1.3 +/-0.2) rats, and the number of neutrop hils/mm(2) of tissue was significantly greater in ARF+IGF-I than in ARF rat s at the corticomedullary junction (52.3 +/-5.2 versus 37.2 +/-4.1) as well as at the renal medulla (172.5 +/- 30.0 versus 42.1 +/-9.6). No other diff erences between the groups were found. It is concluded that IGF-I treatment enhanced the inflammatory response in rats with ischemic ARF. Cell toxicit y derived from increased neutrophil accumulation might play a key role in t he greater mortality risk of critically ill patients that are treated with growth hormone.