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 (1mg/kg/24h s.c.), IGF-I (4mg/kg/24h), or GH in combination with IGF-I over a 48h period. SETTING: Level 1 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.

Dehydroepiandrosterone: a modulator of cellular immunity and heat shock protein 70 production during polymicrobial sepsis.

OBJECTIVE: DHEA is an immunomodulatory steroid hormone that improves survival during systemic inflammation. A DHEA-induced modulation of heat shock protein response may be an alternative mechanism contributing to the beneficial effects of this hormone. We investigated the effect of DHEA administration on survival, cellular immune functions, and HSP-70 production in septic mice. DESIGN AND SETTING: Randomized animal study, level I trauma center, university research laboratory. SUBJECTS: Male NMRI mice. INTERVENTIONS: Mice were subjected to sham operation (laparotomy, LAP) or sepsis (cecal ligation and puncture, CLP) with or without administration of either saline 0.9% (LAP, CLP) or 20 mg/kg DHEA subcutaneously (LAP/DHEA, CLP/DHEA). Survival was monitored over a 48-h period. Splenocyte apoptosis rate (AnnexinV binding), splenocyte proliferation ([3H]thymidine incorporation), TNF-alpha plasma concentration (ELISA), and HSP-70 concentration (ELISA) in tissue extracts from liver, lung, and spleen were monitored 48 h after onset of sepsis. RESULTS: DHEA administration improved the survival of septic mice (78% vs. 50%). This effect was paralleled by increased splenocyte proliferation, decreased cellular apoptosis rate of splenocytes, and attenuation of TNF-alpha release. Furthermore, an increased HSP-70 concentration was observed in lungs and spleens of DHEA-treated septic animals. CONCLUSIONS: DHEA-treatment decreased the mortality rate of septic mice. This was accompanied by improved cellular immune functions and an augmented heat shock response (HSP-70) of lungs and spleens. Further studies are required to demonstrate a direct relationship between the improved survival and the observed alterations in the immune system in DHEA-treated animals.