Survival and cellular immune functions in septic mice treated with growth hormone (GH) and insulin-like growth factor-I (IGF-I)

Objective: GH was used to counteract the catabolic metabolism in critically ill patients until it was demonstrated that administration of GH was associated with an increased morbidity due to uncontrolled infections and sepsis. The immunomodulatory effect of GH and its main mediator IGF-I during systemic inflammation remain to be established. We therefore investigated the effect of GH and IGF-I on cellular immune functions in a murine model of sepsis. Design: Randomized animal study. Septic mice were treated with either saline, GH (1 mg/kg/24 h s.c.), IGF-I (4 mg/kg/24 h), or GH in combination with IGF-I over a 48 It period. Setting: Level I trauma center, university research laboratory. Objects: Male NMRI mice. Measurements: clinical parameters (survival rate, body weight, body temperature, fluid intake, food intake, blood glucose levels) and cellular immune functions (splenocyte proliferation by using a 3 H-thymidine incorporation assay, splenocyte apoptosis by determination of Annexin V binding capacity, splenocyte IL-2, IL-6, and TNF-alpha release by using ELISA, and distribution of circulating immune cell subsets by FACScan). Results: Administration of GH did not affect clinical parameters or cellular immune functions in septic mice. In contrast, treatment with IGF-I alone or in combination with GH improved splenocyte proliferation and increased the ability of splenocytes to release IL-2 and IL-6 without affecting the survival rate or any other clinical parameter determined. Conclusion: GH did not affect cellular immune functions or the survival rate in our murine sepsis model. In contrast, IGF-I improved splenocyte proliferation and cytokine release independently of GH but did not affect the determined clinical parameters of septic mice. (c) 2007 Elsevier Ltd. All rights reserved.