EFFECT OF GRANULOCYTE COLONY-STIMULATING FACTOR ON SYSTEMIC AND PULMONARY RESPONSES TO ENDOTOXIN IN PIGS

Abstract

Granulocyte colony-stimulating factor (G-CSF) stimulates the production and function of neutrophils (PMNs). Administration of G-CSF to non-neutropenic animals has been shown to improve survival in experimental models of infection, but PMNs have been implicated as mediators of acute lung injury induced by lipopolysaccharide (LPS) or bacteremia. Thus G-CSF-induced neutrophilia might be deleterious in sepsis. To investigate this possibility, we studied four groups of pigs: G + E50 (n = 6) were pretreated for 5 days with recombinant bovine (rb) G-CSF (5 μg/kg/day) and then challenged with LPS (50 μg/kg); NS + E50 (n = 6) were similarly pretreated with saline and challenged with LPS (50 μg/kg); E250 (n = 6) were not pretreated and were infused with a larger dose of LPS (250 μg/kg); RL (n = 7) were controls infused with lactated Ringer's solution. Pretreatment with rbG-CSF increased the peripheral absolute neutrophil count approximately fivefold (p < 0.05 vs. RL group). Comparisons of the NS + E50 and G + E50 groups showed that pretreatment with rhG-CSF did not affect LPS-induced alterations in mean arterial blood pressure or arterial oxygenation. Indices of pulmonary injury also were similar in these two groups, although pulmonary edema and protein leakage into alveoli were greater in the E250 group. We conclude that G-CSF-induced neutrophilia does not adversely effect physiologic responses to LPS in pigs.