Granulocyte colony-stimulating factor enhances host defenses against bacterial pneumonia following peritonitis in nonneutropenic rats.
OBJECTIVE
Polymorphonuclear cell functions frequently are impaired in critically ill patients, and restoration of normal functions could help to prevent nosocomial infections. The aim of this study was to evaluate the effects of pretreatment with granulocyte colony-stimulating factor (G-CSF) on bacterial pneumonia induced 48 hrs after peritonitis (cecal ligation and puncture [CLP]) in rats.


METHODS
Controlled animal study.


METHODS
Research laboratory of an academic institution.


METHODS
Male Sprague-Dawley rats.


METHODS
First, the CLP model was characterized. Second, alveolar endotoxin instillation allowed us to evaluate the ability of neutrophils to migrate to airspaces after CLP was assessed. In the last set of experiments, CLP was followed by G-CSF treatment as a preventive therapy for subsequent bacterial superinfection induced by alveolar instillation.


RESULTS
CLP induced a brief increase in proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta) at the 6th hr followed by a longer-lived anti-inflammatory response (interleukin-10 increase from days 1 to 3) in plasma, compared with healthy rats. Impaired neutrophil migration to alveolar spaces denoting immunoparalysis was evidenced after endotracheal endotoxin instillation following CLP, compared with non-CLP rats challenged with endotoxin. No such impairment was found when G-CSF (100 microg/kg: glycosylated recombinant human G-CSF, Lenograstim) was given before endotoxin. G-CSF (100 microg/kg 24 and 48 hrs after CLP) given before endotracheal instillation increased bacterial clearance, as shown by counts in both bronchoalveolar lavage (8.9 x 10 +/- 2.8 x 10 colony-forming units/mL vs. 3.3 x 10 +/- 1.5 x 10 colony-forming units/mL with saline) and lung tissue (4.2 x 10 +/- 1.0 x 10 colony-forming units/g vs. 1.5 x 10 +/- 0.6 x 10 colony-forming units/g with saline). Furthermore, G-CSF pretreatment kept clearance in CLP rats similar to that in non-CLP rats challenged with.


CONCLUSIONS
These results suggest that G-CSF (Lenograstim) may enhance host defenses in rats with peritonitis and immunoparalysis.
D000818:Animals; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D010538:Peritonitis / Q000150:complications*; D018410:Pneumonia, Bacterial / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D011552:Pseudomonas Infections / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016179:Granulocyte Colony-Stimulating Factor