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 severe trauma is the alteration in concentrations of a large number of plasma proteins referred to as acute-phase proteins (APP). The principle mediators of these liver-synthesized APP are mainly the cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha).


METHODS
We have measured the plasma levels of IL-6, TNF alpha, and 20 APP in 24 adult, severely injured, hypermetabolic and highly catabolic patients with multiple injuries within 48-60 hours after injury, when they 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 trauma include C-reactive protein (CRP), alpha-1 antichymotrypsin, alpha-1 acid glycoprotein, alpha-1 antitrypsin, fibronectin, and factor B. Negative APP include IgG, IgM, complement-3, prealbumin, transferrin, ceruloplasmin, and albumin. Except for CRP, alpha-1 antichymotrypsin, and albumin, all the APP levels increase during 7 days of nutritional support. Plasma levels of cytokines IL-6 and TNF-alpha, although initially markedly increased after injury, decrease with parenteral refeeding. There is a linear correlation between CRP and IL-6 levels and also between the transport proteins prealbumin and transferrin. Trauma-induced increases in CRP and IL-6 levels decreased with nutrition alone, but did not change with rhGH supplementation. An immunosuppressed state of injury is evident from the decreased immunoglobulin levels (IgG, IgM, IgA) in the trauma patients. Total parenteral nutrition alone increases the immunoglobulin levels to normal. However, with adjuvant rhGH, only IgA levels are normalized.


CONCLUSIONS
Adjuvant rhGH therapy does not attenuate the reprioritization of acute liver protein synthesis and results in only limited restoration of host defenses. The clinical implications of these findings await further study.
Petersen
S R
SR
Trauma Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85013, USA.
Jeevanandam
M
M
Shahbazian
L M
LM
Holaday
N J
NJ
D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D013006:Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009104:Multiple Trauma / Q000097:blood / Q000378:metabolism*; D010289:Parenteral Nutrition, Total; D011228:Prealbumin / Q000032:analysis; D014168:Transferrin / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D000209:Acute-Phase Proteins; D015850:Interleukin-6; D011228:Prealbumin; D014168:Transferrin; D014409:Tumor Necrosis Factor-alpha; D013006:Growth Hormone; D002097:C-Reactive Protein