T. Muto

Growth Hormone and the Immune Response to Bacterial Infection

Growth hormone (GH) and insulin-like growth factor 1 (IGF-1), especially the former, have immunoregulatory effects in addition to anabolic effects. The hormones may act to protect the host from lethal bacterial infection by promoting the maturation of myeloid cells, stimulating phagocyte migration, priming phagocytes for the production of superoxide anions and cytokines, and enhancing opsonic activity. GH administration may be beneficial for the prevention, as well as treatment, of severe sepsis in critical illness.

Glutamine-Enriched Enteral Diet Enhances Bacterial Clearance in Protracted Bacterial Peritonitis, Regardless of Glutamine Form‡

BACKGROUND The effects of glutamine (Gln)-enriched enteral diets on bacterial clearance were investigated in a rat protracted peritonitis model. The effects of the Gln form, peptide-based vs free amino acid-based, were also compared. METHODS Twenty-three rats underwent gastrostomy. An osmotic pump was implanted in the peritoneal cavity. The rats received a continuous intragastric infusion of one of three diets: Gln-depleted (Gln 0), Gln-enriched with the Gln in free amino acid form (Gln F), or Gln-enriched with the Gln in oligopeptide form (Gln P). The three formulas were isocaloric and isonitrogenous. The pumps delivered a continuous infusion of Escherichia coli, starting at 48 hours after implantation, for 24 hours. Then, the animals were killed. RESULTS Bacterial numbers in peritoneal lavaged fluid (PLF) and the liver were significantly lower in the Gln P and Gln F groups than in the Gln 0 group. The bacterial number in PLF correlated with that in the liver. Neither the number nor the population of peritoneal exudative cells differed among groups. Plasma levels of proline, alanine and citrulline were significantly higher in the Gln P and Gln F groups than in the Gln 0 group. Both Gln supplemented groups showed significantly greater villous height, crypt depth, and numbers of mitoses per crypt in the small intestine than the Gln 0 group. CONCLUSIONS Supplemental Gln enhances peritoneal and hepatic bacterial clearance, regardless of Gln form. Gln-enriched may be more beneficial than Gln-depleted enteral diets in peritonitis.

GROWTH HORMONE AND INSULIN-LIKE GROWTH FACTOR I AUGMENT ESCHERICHIA COLI-KILLING ACTIVITY OF MURINE PERITONEAL EXUDATIVE CELLS

Effects of growth hormone (GH) and insulin-like growth factor (IGF)-I on Escherichia coli-killing activity of murine peritoneal exudative cells (PECs) were investigated. Plasma from the mice, injected subcutaneously with saline, GH (4.8 mg/kg/day), or IGF-I (24 mg/kg/day) for 6 days, was mixed with E. coli and pooled murine PECs. Plasma from GH- and IGF-l-treated mice modestly but significantly augmented the E. co//-killing activity of PECs, as compared with that from saline controls. Plasma from IGF-l-treated mice also enhanced PEC interleukin 1 production. In the next experiment, PECs preincubated with medium, GH (10–1000 ng/mL), or IGF-I (50–5000 ng/mL) for 3 h were investigated for E co//-killing activity. Preincubation of PECs with all concentrations of GH and IGF-I significantly enhanced the E. co//-killing activity of PECs, as compared with the medium control. These results indicate that GH and IGF-I enhance phagocytosis and the E. co//-killing activity of PECs, via a modestly increased plasma capacity to support these activities, as well as by a strong direct action.

Effects of Growth Hormone and Insulin-Like Growth Factor 1 (IGF-1) Treatments on the Nitrogen Metabolism and Hepatic IGF-1-Messenger RNA Expression in Postoperative Parenterally Fed Rats

BACKGROUND Few studies have made direct comparisons of the metabolic effects of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). We have assessed the dose-dependent effects of GH and IGF-1 treatments on nitrogen metabolism, intestinal structure, and hepatic IGF-1-messenger RNA (mRNA) expression in postoperative parenterally fed rats. METHODS Rats were maintained on total parenteral nutrition (TPN) for 3 days after gastrectomy. GH (0.4 or 0.8 IU/kg/d) or IGF-1 (1,2, or 4 mg/kg/d) was infused throughout the experimental period. Anabolic effects of GH and IGF-1 were assessed by body weight change, nitrogen excretion, and whole-body protein turnover. Organ weights, intestinal structure, plasma IGF-1 levels and hepatic IGF-1-mRNA contents were also determined. RESULTS Both GH and IGF-1 attenuated body weight loss and nitrogen excretion and increased whole-body protein synthesis and spleen weight. These observations suggest that the anabolic effects of 1 mg/kg/d of IGF-1 were equivalent to those of 0.66 IU/kg/d of GH. IGF-1, but not GH, reduced atrophy of the intestinal mucosa. GH treatment increased hepatic IGF-1-mRNA and the plasma IGF-1 level, whereas IGF-1 treatment increased the plasma IGF-1 level with no change in the hepatic IGF-1-mRNA content. CONCLUSIONS Administration of GH or IGF-1 attenuates catabolism after surgery. The anabolic effects of 1 mg/kg/d of IGF-1 are equivalent to those of 0.66 IU/kg/d of GH. IGF-1 reduces intestinal mucosal atrophy. GH increases hepatic IGF-1-mRNA and the plasma IGF-1 level.

Effects of growth hormone and insulin-like growth factor 1 (IGF-1 ) on hepatic IGF-1-mRNA, plasma IGF-1 and nitrogen excretion in gastrectomized rats with liver cirrhosis

The growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis is impaired in liver cirrhosis. We determined the effects of GH and IGF-1 treatments in gastrectomized rats with thioacetamide-induced cirrhosis. GH did not increase hepatic IGF-1-mRNA, plasma IGF-1 or the tissue, i.e. gastrocnemius muscle IGF-1 level. IGF-1 administration increased plasma IGF-1 without increasing hepatic IGF-1-mRNA. GH and IGF-1 independently decreased postoperative urinary nitrogen excretion. We conclude that both GH and IGF-1 improve postoperative nitrogen metabolism. Furthermore, GH may exert its anabolic effects directly and/or via actions mediated by IGF-1 production, other than in the liver and in the skeletal muscle, in the setting of cirrhosis.

O.45 Effects of growth hormone and insulin-likegrowth factor 1 on PMN phagocytosis and monocyte HLA-DR expression in postoperative patients

blanace between secretion from the liver and degradation mainly in the kidney. Effects of severe trauma on plasma GSH levels are not known. Aim: To measure the altered plasma levels of GSH due to severe injury and their changes due to TPN with or without rhGH in trauma victims. Methods: Plasma levels of total GSH (pM, enzymatic recycling procedure) in 14 post-absorptive normals and 24 severely injured (ISS = 31 _+ 2), hypermetabolic (REE = 1.28 + 0.04 BEE) and hypercataboiic patients once within 48-60 hrs after injury when they were receiving maintenance fluids with no calorie or N and again after 3 and 7 days of TPN with (n = 12, Group H) or without (n = 12, Group C) rhGH (0.15 mg/kg/d). Results: GSH plasma levels in trauma patients (1.52 _+ 0.18 pM) under basal conditions (day 0) are not significantly different from uninjured normals (1.67 _+ 0.17pM), showing that severe injury has little or no effect on plasma GSH levels. The time course of the changes in plasma GSH in trauma victims are (mean _+ SEM, pM):