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 serve s as one of the body's most important defenses against oxygen metabolites. Plasma levels of GSH are maintained primarily by a balance between secretio n 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 se vere 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 cy tokines 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 postab sorptive 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 fo r basal, plasma GSH, TNF-alpha, and IL-6 measurement. Intravenous feeding w as then started and continued for 7 days. The patients were randomized to r eceive or not to receive daily intramuscular doses of recombinant human gro wth hormone (0.15 mg rhGH/kg/day). Daily morning plasma was obtained for an alysis of GSH, TNF-alpha, and IL-6 levels. Results: In the early catabolic "flow phase" of severe injury, the plasma l evels of GSH were not altered but plasma TNF-alpha and IL-6 levels were inc reased 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-supplemen ted trauma patients. Conclusion: Modification of plasma GSH and TNF-alpha levels by adequate nut ritional support with adjuvant rhGH during the postinjury period demonstrat es the beneficial role of GSH in enhancing antioxidant defenses.