Altered plasma cytokines and total glutathione levels in parenterally fed critically ill trauma patients with adjuvant recombinant human growth hormone (rhGH) therapy

Objectives: Glutathione (GSH) is a potent endogenous antioxidant that serves as one of the body's most important defenses against oxygen metabolites. Plasma levels of GSH are maintained primarily by a balance between secretion from the liver and degradation in the kidney. The ability to maintain and enhance tissue GSH may be of particular importance in controlling cytokine production in response to a stimulus like injury. The interaction after severe trauma between GSH and cytokines, tumor necrosis factor (TNF) -alpha, and interleukin (IL)-6, are not known. The purpose of the study was to investigate the levels of plasma GSH and cytokines TNF-alpha and IL-6 in adult patients admitted to the intensive care unit of our level I trauma center who were treated with recombinant human growth hormone (rhGH) for greater than or equal to 7 days. Design: Prospective, randomized, controlled trial. Setting: Trauma intensive care unit. Patients: Twenty-eight patients with multiple injuries and 14 normal postabsorptive controls. Interventions: From 48-60 hrs after injury, when resuscitation was complete, a stable hemodynamic status was achieved and the patients were receiving maintenance fluid without nitrogen or calories, a blood sample was drawn for basal, plasma GSH, TNF-alpha, and IL-6 measurement. Intravenous feeding was then started and continued for 7 days. The patients were randomized to receive or not to receive daily intramuscular doses of recombinant human growth hormone (0.15 mg rhGH/kg/day). Daily morning plasma was obtained for analysis of GSH, TNF-alpha, and IL-6 levels. Results: In the early catabolic "flow phase" of severe injury, the plasma levels of GSH were not altered but plasma TNF-alpha and IL-6 levels were increased significantly, compared with uninjured controls. Seven days of total parenteral nutrition alone enhanced plasma GSH levels (76%), hut no change in TNF-alpha was observed. Supplementation with rhGH enhanced GSH (180%), and TNF (65%) with no changes in IL-6 levels. There is a significant linear relationship between plasma GSH and TNF-alpha levels in our rhGH-supplemented trauma patients. Conclusion: Modification of plasma GSH and TNF-alpha levels by adequate nutritional support with adjuvant rhGH during the postinjury period demonstrates the beneficial role of GSH in enhancing antioxidant defenses.