Changes in circulating insulin-like growth factor-I, insulin-like growth factor binding proteins, and leptin in...

One of the hallmarks of the pathophysiology of enteric disease in young pigs is reduced growth performance. This reduction in growth is associated with changes in the endocrine somatotropic growth axis. Our laboratory previously demonstrated that circulating insulin-like growth factor-I (IGF-I) was reduced in pigs infected with Salmonella enterica serovar Typhimurium (S. typhimurium) while circulating growth hormone remained unchanged. The objective of the current study was to determine if infection with S. typhimurium also was associated with changes in circulating IGF binding proteins (IGFBP). In addition, pigs experiencing active enteric disease have reduced feed intake. Because this inappetence may be related to systemic appetite reduction signals, we also evaluated circulating leptin in pigs undergoing active S. typhimurium-induced enteric disease. Crossbred pigs were penned in environmentally controlled rooms with free access to feed and water. Following an acclimation period, pigs were gavaged with 10(10) cfu of S. typhimurium (SAL; n=6) or were given a similar volume of sterile growth media (CON; n=6). Rectal temperatures and feed intakes were measured daily through 168 h to track the time course of the response to S. typhimurium infection. Samples of serum were obtained by jugular venipuncture at 0, 24, 48, 96 and 168 h after infection. Sera were frozen until evaluation for IGF-I by immunoradiometric assay (IRMA). In addition, sera were subjected to western ligand blotting utilizing 125I-IGF-I and 125I-IGF-II. Images were evaluated for total IGFBP and IGFBP-3 by densitometric analyses. Rectal temperature was increased in SAL pigs 24h post-infection (P<0.001) but not at other times. Feed intake was reduced in SAL pigs during the intervals 24-72 h (P<0.001) and 96-144 h (P<0.05) after infection. Serum IGF-I, expressed as a percentage of the 0 h concentration, was reduced in SAL pigs versus CON pigs at 48 h (28.1+/-18.7% versus 102.2+/-17.1%; P<0.01) and 96 h (20.0+/-18.7% versus 128.4+/-17.0%; P<0.0001) post-infection. Both total IGFBP and IGFBP-3, as estimated by ligand blotting, also were reduced in infected pigs at 48 h postchallenge (P<0.05). IGFBPs were similar between the two treatments at other sampling times. Concentrations of IGFBP-3 also were estimated utilizing an IRMA for human IGFBP-3. Serum IGFBP-3 was reduced in S. typhimurium-infected pigs at 24 h (P<0.01), 48 h (P<0.001), 96 h (P<0.001), and 168 h (P<0.05). Serum leptin levels were similar between SAL and CON pigs. The data suggest that swine enteric disease is associated with reduced circulating IGF-I and reductions in total IGFBP and IGFBP-3. However, serum leptin was not affected by enteric disease challenge.