Growth hormone increases circulating neutrophil activation and provokes lung microvascular injury in septic peritonitis rats.

BACKGROUND Growth hormone (GH) has been shown to increase mortality in critical illness, illustrating the need for better understanding of GH treatment. The neutrophil is a key mediator in producing organ injury following shock and trauma and is regulated by GH. Therefore, the purpose of the present study was to examine the effects of GH on circulating neutrophil activation and subsequent lung injury induced by sepsis in rats. MATERIALS AND METHODS Sepsis was induced in male Wistar rats via cecal ligation and puncture (CLP). Recombinant human growth hormone (1 IU/kg) was given subcutaneously right after CLP with an additional injection at 12 h after CLP. CD11b expression and an oxidative burst of neutrophils were detected using flow cytometric analysis. Lung myeloperoxidase activity was determined as an index of tissue neutrophil accumulation. Lung microvascular injury was assessed by quantitating extravasation of Evan's blue dye into lung parenchyma. RESULTS Growth hormone significantly increased sepsis-induced expression of CD11b and sepsis-induced circulating neutrophil activation. Also growth hormone increased neutrophil accumulation in lungs induced by sepsis. Lung microvascular injury was aggravated by growth hormone treatment in septic rats. CONCLUSIONS It is worthwhile to rethink GH administration in critical illness and further studies are required to determine the safety and clinical benefits of GH administration in critical illness.

[1]  J. Pierce,et al.  Reactive oxygen species in acute respiratory distress syndrome. , 2001, Heart & lung : the journal of critical care.

[2]  A. Malik,et al.  Decreased oxidant buffering impairs NF-kappaB activation and ICAM-1 transcription in endothelial cells. , 2001, Shock.

[3]  S. Tasaka,et al.  CD11/CD18-dependent and -independent neutrophil emigration in the lungs: how do neutrophils know which route to take? , 2000, American journal of respiratory cell and molecular biology.

[4]  E. Abraham.  NF-κB activation , 2000 .

[5]  A. L. Jensen,et al.  Characterization of the Priming Effect by Pituitary Canine Growth Hormone on Canine Polymorphonuclear Neutrophil Granulocyte Function , 2000, Clinical Diagnostic Laboratory Immunology.

[6]  G. Van den Berghe,et al.  Increased mortality associated with growth hormone treatment in critically ill adults. , 2000, The New England journal of medicine.

[7]  K. Fukatsu,et al.  Growth hormone inhibits apoptosis and up-regulates reactive oxygen intermediates production by human polymorphonuclear neutrophils. , 1998, JPEN. Journal of parenteral and enteral nutrition.

[8]  R. Barrow,et al.  Growth hormone treatment in pediatric burns: a safe therapeutic approach. , 1998, Annals of surgery.

[9]  E. Chilvers,et al.  Neutrophil priming: pathophysiological consequences and underlying mechanisms. , 1998, Clinical science.

[10]  R. Bone,et al.  Sepsis: a new hypothesis for pathogenesis of the disease process. , 1997, Chest.

[11]  W. Cheadle,et al.  Poor outcome from peritonitis is caused by disease acuity and organ failure, not recurrent peritoneal infection. , 1997, Annals of surgery.

[12]  C. Smith,et al.  Mechanisms of neutrophil‐induced parenchymal cell injury , 1997, Journal of leukocyte biology.

[13]  L. Balteskard,et al.  Growth hormone impaired compensation of hemorrhagic shock after trauma and sepsis in swine. , 1996, The Journal of trauma.

[14]  J. Christman,et al.  In vivo antioxidant treatment suppresses nuclear factor-kappa B activation and neutrophilic lung inflammation. , 1996, Journal of immunology.

[15]  E. Moore,et al.  CD11b blockade prevents lung injury despite neutrophil priming after gut ischemia/reperfusion. , 1995, The Journal of trauma.

[16]  E. Moore,et al.  Postinjury neutrophil priming and activation states: therapeutic challenges. , 1995, Shock.

[17]  P. Cole,et al.  Growth hormone is a human macrophage activating factor. Priming of human monocytes for enhanced release of H2O2. , 1995, Journal of immunology.

[18]  D. Wilmore,et al.  Increased survival after major thermal injury: the effect of growth hormone therapy in adults. , 1995, The Journal of trauma.

[19]  E. Moore,et al.  The postischemic gut serves as a priming bed for circulating neutrophils that provoke multiple organ failure. , 1994, The Journal of trauma.

[20]  T. Carlos,et al.  Leukocyte-endothelial adhesion molecules. , 1994, Blood.

[21]  S. Chang,et al.  Evans blue dye in the assessment of permeability-surface area product in perfused rat lungs. , 1994, Journal of applied physiology.

[22]  C. Smith,et al.  Role of beta 2 integrins and ICAM-1 in lung injury following ischemia-reperfusion of rat hind limbs. , 1993, The American journal of pathology.

[23]  J. Parrillo.  Pathogenetic mechanisms of septic shock. , 1993, The New England journal of medicine.

[24]  C. Wiedermann,et al.  In vitro activation of neutrophils of the aged by recombinant human growth hormone. , 1991, The Journal of infectious diseases.

[25]  D. Geissler,et al.  Priming of normal human neutrophils by recombinant human growth hormone , 1991, British journal of haematology.

[26]  S. Arkins,et al.  A novel role of growth hormone and insulin-like growth factor-I. Priming neutrophils for superoxide anion secretion. , 1991, Journal of immunology.

[27]  A. Benzer,et al.  Improvement of septic syndrome after administration of recombinant human growth hormone (rhGH)? , 1991, The Journal of trauma.

[28]  M. Fink,et al.  Laboratory models of sepsis and septic shock. , 1990, The Journal of surgical research.

[29]  S. Weiss.  Tissue destruction by neutrophils. , 1989, The New England journal of medicine.

[30]  K. Kelley,et al.  A newly defined property of somatotropin: priming of macrophages for production of superoxide anion. , 1988, Science.

[31]  B. Meyrick,et al.  Direct effects of E coli endotoxin on structure and permeability of pulmonary endothelial monolayers and the endothelial layer of intimal explants. , 1986, The American journal of pathology.

[32]  W. Stenson,et al.  Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. , 1984, Gastroenterology.

[33]  M. Seeds,et al.  Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. , 1983, Journal of immunology.

[34]  K. Brigham,et al.  Increased Sheep Lung Vascular Permeability Caused by Escherichia coli Endotoxin , 1979, Circulation research.