Key result
Depletion of pulmonary intravascular macrophages with gadolinium chloride 48 hours prior to E. coli lipopolysaccharide challenge resulted in 100% survival at 6 hours, compared to 100% mortality in untreated bile-duct ligated rats.
Why the study?
Does gadolinium chloride-induced depletion of pulmonary intravascular macrophages prevent endotoxin-induced mortality and lung inflammation in a rat model of hepato-pulmonary syndrome?
Does gadolinium chloride-induced depletion of pulmonary intravascular macrophages prevent endotoxin-induced mortality and lung inflammation in a rat model of hepato-pulmonary syndrome?
Depletion or inactivation of pulmonary intravascular macrophages with gadolinium chloride protects against endotoxin-induced mortality and lung inflammation in a rat model of hepato-pulmonary syndrome.
Answers are grounded in this paper and cite their sources.
Protects against endotoxin mortality in this rat model; leaves open whether pulmonary macrophage depletion translates to patients.
BACKGROUND: Bile-duct ligated (BDL) rats recruit pulmonary intravascular macrophages (PIMs) and are highly susceptible to endotoxin-induced mortality. The mechanisms of this enhanced susceptibility and mortality in BDL rats, which are used as a model of hepato-pulmonary syndrome, remain unknown. We tested a hypothesis that recruited PIMs promote endotoxin-induced mortality in a rat model. METHODS: Rats were subjected to BDL to induce PIM recruitment followed by treatment with gadolinium chloride (GC) to deplete PIMs. Normal and BDL rats were treated intravenously with E. coli lipopolysaccharide (LPS) with or without GC pre-treatment followed by collection and analyses of lungs for histopathology, electron microscopy and cytokine quantification. RESULTS: BDL rats recruited PIMs without any change in the expression of IL-1beta, TNF-alpha and IL-10. GC caused reduction in PIMs at 48 hours post-treatment (P < 0.05). BDL rats treated intravenously with E. coli LPS died within 3 hours of the challenge while the normal LPS-treated rats were euthanized at 6 hours after the LPS treatment. GC treatment of rats 6 hours or 48 hours before LPS challenge resulted in 80% (1/5) and 100% (0/5) survival, respectively, at 6 hours post-LPS treatment. Lungs from BDL+LPS rats showed large areas of perivascular hemorrhages compared to those pre-treated with GC. Concentrations of IL-1beta, TNF-alpha and IL-10 were increased in lungs of BDL+LPS rats compared to BDL rats treated with GC 48 hours but not 6 hours before LPS (P < 0.05). CONCLUSION: We conclude that PIMs increase susceptibility for LPS-induced lung injury and mortality in this model, which is blocked by a reduction in their numbers or their inactivation.
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Gill et al. (2008) studied Endotoxin-induced lung inflammation and mortality (hepato-pulmonary syndrome model) (n=41). Gadolinium chloride (GC) vs. No GC pre-treatment (BDL + LPS) was evaluated on Mortality at 6 hours post-LPS challenge (p=<0.05). Depletion of pulmonary intravascular macrophages with gadolinium chloride 48 hours prior to E. coli lipopolysaccharide challenge resulted in 100% survival at 6 hours, compared to 100% mortality in untreated bile-duct ligated rats.
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