Endotoxin decreases serum IGFBP-3 and liver IGFBP-3 mRNA: comparison between Lewis and Wistar rats.

We studied the IGFBP-3 response to endotoxin, in Wistar and Lewis rats. Compared to Wistar rats, Lewis rats have a reduced adrenal and IGF-I response to inflammatory stimuli. Rats received two injections of 1 mg/kg of lipopolysaccharide (LPS) and were killed 4 h after the second injection. LPS decreased serum concentrations of GH in Wistar (P<0.05), but not in Lewis rats. However, serum IGFBP-3 was decreased both in Wistar and in Lewis rats. Furthermore, LPS administration decreased IGFBP-3 gene expression in the liver in both rat strains (P<0.01). Lewis rats had lower serum IGFBP-3 than Wistar rats (P<0.01). This difference could be secondary to the increased IGFBP-3 proteolysis in serum observed in Lewis rats. These data indicate that acute inflammation inhibits serum concentrations of IGFBP-3 by decreasing its synthesis in the liver, rather than increasing its proteolysis. This effect seems to be GH and IGF-I independent.