Related Experiment Videos
Effect of granulocyte colony-stimulating factor on systemic and pulmonary responses to endotoxin in pigs
M P Fink1, B P O'Sullivan, M J Menconi
1Department of Surgery, University of Massachusetts Medical Center, Worcester.
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 micrograms/kg/day) and then challenged with LPS (50 micrograms/kg); NS+E50 (n = 6) were similarly pretreated with saline and challenged with LPS (50 micrograms/kg); E250 (n = 6) were not pretreated and were infused with a larger dose of LPS (250 micrograms/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.
Insights
Granulocyte colony-stimulating factor (G-CSF) pretreatment did not worsen physiological responses to lipopolysaccharide (LPS) in pigs. G-CSF-induced neutrophilia did not adversely affect blood pressure or oxygenation during LPS challenge.
Area of Science:
- Immunology
- Critical Care Medicine
- Pulmonary Medicine
Background:
- Granulocyte colony-stimulating factor (G-CSF) promotes neutrophil production and function.
- Neutrophils mediate acute lung injury, raising concerns about G-CSF's role in sepsis.
- G-CSF-induced neutrophilia might be detrimental in sepsis models.
Purpose of the Study:
- To investigate the potential adverse effects of G-CSF-induced neutrophilia in a porcine model of sepsis.
- To determine if G-CSF pretreatment exacerbates lipopolysaccharide (LPS)-induced physiological changes.
Main Methods:
- Four groups of pigs were studied: G-CSF pretreated + LPS, saline pretreated + LPS, high-dose LPS only, and control.
- G-CSF (5 µg/kg/day) or saline was administered for 5 days prior to LPS challenge.
- Physiological parameters including mean arterial blood pressure and arterial oxygenation were monitored.
Main Results:
- G-CSF pretreatment significantly increased peripheral neutrophil counts (neutrophilia).
- No significant differences in blood pressure or oxygenation were observed between G-CSF pretreated and saline pretreated groups following LPS challenge.
- Pulmonary injury indices were similar between these two groups, though higher in the high-dose LPS group.
Conclusions:
- G-CSF-induced neutrophilia does not appear to adversely affect acute physiological responses to LPS in pigs.
- The findings suggest G-CSF may not be detrimental in the context of LPS-induced sepsis.
- Further research is warranted to fully elucidate G-CSF's role in sepsis pathophysiology.