Acute G-CSF therapy is not protective during lethal E-coli sepsis

We investigated whether decreases in circulating polymorphonuclear neutroph ils (PMN) during lethal Escherichia coli (E. coli) sepsis in canines are re lated to insufficient host granulocyte colony-stimulating factor (G-CSF). T wo-year-old purpose-bred beagles had intraperitoneal E. coli-infected or -n oninfected fibrin clots surgically placed. By 10 to 12 h following clot, bo th infected survivors and nonsurvivors had marked increases (P = 0.001) in serum G-CSF levels (mean peak G-CSF ng/ ml +/- SE, 1,931 +/- 364 and 2,779 +/- 681, respectively) compared with noninfected controls (134 +/- 79), whi ch decreased at 24 to 48 h. Despite increases in G-CSF, infected clot place ment caused delayed (P = 0.06) increases in PMN (mean +/- SE change from ba seline in cells x 10(3)/mm(3) at 24 and 48 h) in survivors (+3.9 +/- 3.9 an d +13.8 +/- 3.6) compared with noninfected controls (+13.1 +/- 2.8 and +9.1 +/- 2.5). Furthermore, infected nonsurvivors had decreases in PMN (-1.4 +/ - 1.0 and -1.1 +/- 2.3, P = 0.006 compared with the other groups). We next investigated whether administration of G-CSF immediately after clot placeme nt and continued for 96 h to produce more rapid and prolonged high levels o f G-CSF after infection would alter PMN levels. Although G-CSF caused large increases in PMN compared with control protein from 2 to 48 h following cl ot in noninfected controls, it caused much smaller increases in infected su rvivors and decreases in infected nonsurvivors (P = 0.03 for the ordered ef fect of G-CSF comparing the three groups). Thus insufficient host G-CSF is unlikely the cause of decreased circulating PMN in this canine model of sep sis. Other factors associated with sepsis either alone or in combination wi th G-CSF itself may reduce increases or cause decreases in circulating PMN.