REPRIORITIZATION OF LIVER PROTEIN-SYNTHESIS RESULTING FROM RECOMBINANT HUMAN GROWTH-HORMONE SUPPLEMENTATION IN PARENTERALLY FED TRAUMA PATIENTS - THE EFFECT OF GROWTH-HORMONE ON THE ACUTE-PHASE RESPONSE

Background: One of the major components of the metabolic response to s evere trauma is the alteration in concentrations of a large number of plasma proteins referred to as acute-phase proteins (APP). The princip le mediators of these liver-synthesized APP are mainly the cytokines i nterleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). Metho ds: We have measured the plasma levels of IL-6, TNF alpha, and 20 APP in 24 adult, severely injured, hypermetabolic and highly catabolic pat ients with multiple injuries within 48-60 hours after injury, when the y were receiving maintenance fluids without calories or nitrogen, and subsequently during 7 days of total parenteral nutrition with (n = 12) or without (n = 12) recombinant human growth hormone supplementation (rhGH, 0.15 mg/kg/d). Results: Baseline positive APP due to severe tra uma include C-reactive protein (CRP), alpha-1 antichymotrypsin, alpha- 1 acid glycoprotein, alpha-1 antitrypsin, fibronectin, and factor B. N egative APP include IgG, IgM, complement-3, prealbumin, transferrin, c eruloplasmin, and albumin. Except for CRP, alpha-1 antichymotrypsin, a nd albumin, all the APP levels increase during 7 days of nutritional s upport. Plasma levels of cytokines IL-6 and TNF-alpha, although initia lly markedly increased after injury, decrease with parenteral refeedin g. There is a linear correlation between CRP and IL-6 levels and also between the transport proteins prealbumin and transferrin. Trauma-indu ced increases in CRP and IL-6 levels decreased with nutrition alone, b ut did not change with rhGH supplementation. An immunosuppressed state of injury is evident from the decreased immunoglobulin levels (IgG, I gM, IgA) in the trauma patients. Total parenteral nutrition alone incr eases the immunoglobulin levels to normal. However, with adjuvant rhGH , only IgA levels are normalized. Conclusions: Adjuvant rhGH therapy d oes not attenuate the reprioritization of acute liver protein synthesi s and results in only limited restoration of host defenses. The clinic al implications of these findings await further study.