GRANULOCYTE-COLONY-STIMULATING FACTOR IMPROVES HOST-DEFENSE TO RESUSCITATED SHOCK AND POLYMICROBIAL SEPSIS WITHOUT PROVOKING GENERALIZED NEUTROPHIL-MEDIATED DAMAGE

Background: Granulocyte colony-stimulating factor (G-CSF) increases pr oduction and release of neutrophil precursors and activates multiple f unctions of circulating polymorphonuclear neutrophils (PMNs), G-CSF ha s therapeutic effects in many experimental models of sepsis; its actio ns with superimposed reperfusion insults are unknown. In traumatic con ditions, G-CSF could exacerbate unregulated, PMN-dependent injury to o therwise normal host tissue or, it could partially reverse trauma-indu ced immune suppression, which may improve long-term outcome. This stud y tested whether stimulating PMN proliferation and function with G-CSF during recovery from trauma+sepsis potentiated reperfusion injury or whether it improved host defense. Methods: Anesthetized swine were sub jected to cecal ligation and incision, 35% hemorrhage, and 1 hr of hyp otension. Resuscitation consisted of intravenous G-CSP (5 mu g/kg) or placebo followed by shed blood and 40 mL/kg of lactated Ringer's solut ion. The control group received laparotomy only. G-CSF or placebo was given daily. Animals were killed at 4 days. Observers, blind to the pr otocol, graded autopsy samples for localization of infection and quali ty of abscess wall formation. Data included complete blood count, gran ulocyte oxidative burst after phorbol myristate acetate stimulation in vitro (GO(2)B), bronchoalveolar lavage (BAL) cell count, BAL noncellu lar protein, lipopolysaccharide-stimulated tumor necrosis factor produ ction in whole blood in vitro(lipopolysaccharide-tumor necrosis factor ), and lung tissue myeloperoxidase (MPO). Results: Neutrophilia and lo calization of infection, were sig nificantly improved by G-CSF. Variab les altered by G-CSF, though mot significantly, showed GO(2)B potentia l increased by 50%, lipopolysaccharide-tumor necrosis factor decreased by 50%, and improved survival versus placebo (100% vs. 70%). G-CSF di d not increase lung MPO, BAL cell count, of BAL protein. Both arterial and venous O-2 saturations were unaltered. Conclusions: Our data show that G-CSF initiated at the time of resuscitation reduced the sequela e of posttrauma sepsis by increasing PMN proliferation and function wi thout potentiating PMN-mediated lung reperfusion injury.