Growth hormone and insulinlike growth factor I enhance host defense in a murine sepsis model

T. Inoue, H. Saito, R. Fukushima, T. Inaba, M. T. Lin, K. Fukatsu and T. Muto
Department of Surgery, University of Tokyo, Japan.

OBJECTIVE: To investigate the effects of exogenous growth hormone (GH) and insulinlike growth factor I (IGF-I) on host defense and survival in a murine model of Escherichia coli sepsis. DESIGN: Prospective randomized experimental trials. SETTING: Laboratory. MATERIALS: Nine-week-old female BALB/c mice. INTERVENTIONS: Mice were injected subcutaneously with 4.8 or 0.48 mg/kg of body weight per day of GH, 24 or 2.4 mg/kg of body weight per day of IGF-I or, as a control, normal saline solution, for 6 days. Mice were then challenged intraperitoneally with 1 x 10(8) colony-forming units per body of E coli. MAIN OUTCOME MEASURES: Fifty mice were observed for survival. In the next experiments, samples from the high-dose GH, high-dose IGF-I, and saline control groups were harvested before or at 4 or 6 hours after challenge. Numbers of peritoneal exudative cells and tissue-viable bacterial counts were determined. Peritoneal exudative cells were cultured with lipopolysaccharide (10 micrograms/mL) for 24 hours. Levels of tumor necrosis factor, interleukin-1, and interleukin-6 in the peritoneal lavage fluid, plasma and supernatants of peritoneal exudative cell culture were measured. RESULTS: Both high and low doses of GH and high-dose IGF-I significantly prolonged survival. Growth hormone and IGF-I significantly increased peritoneal exudative cell numbers and reduced viable bacterial counts in the peritoneal lavage fluid and the liver. These hormones significantly suppressed excessive systemic cytokine production, while enhancing in vitro cytokine production and preserving local cytokine responses. CONCLUSION: The immunomodulation produced by administration of GH or IGF-I leads to improved host defense in this murine model of E coli sepsis.

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