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Transl Res. 2008 Nov;152(5):213-24. doi: 10.1016/j.trsl.2008.09.002. Epub 2008 Oct 11.

Sphingosine 1-phosphate rescues canine LPS-induced acute lung injury and alters systemic inflammatory cytokine production in vivo.

Author information

1
Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

Abstract

S1P has been demonstrated to protect against the formation of lipopolysaccharide (LPS)-induced lung edema when administered concomitantly with LPS. In the current study, we sought to determine the effectiveness of S1P to attenuate lung injury in a translationally relevant canine model of ALI when administered as rescue therapy. Secondarily, we examined whether the attenuation of LPS-induced physiologic lung injury after administration of S1P was, at least in part, caused by an alteration in local and/or systemic inflammatory cytokine expression. We examined 18, 1-year-old male beagles prospectively in which we instilled bacterial LPS (2-4 mg/kg) intratracheally followed in 1 h with intravenous S1P (85 microg/kg) or vehicle and 8 h of high-tidal-volume mechanical ventilation. S1P attenuated the formation of Q(s)/Q(t) (32%), and both the presence of protein (72%) and neutrophils (95%) in BAL fluid compared with vehicle controls. Although lung tissue inflammatory cytokine production was found to vary regionally throughout the LPS-injured lung, S1P did not alter the expression pattern. Similarly, BAL cytokine production was not altered significantly by intravenous S1P in this model. Interestingly, S1P potentiated the LPS-induced systemic production of 3 inflammatory cytokines, TNF-alpha (6-fold), KC (1.2-fold), and IL-6 (3-fold), without resulting in end-organ dysfunction. In conclusion, intravenous S1P reduces inflammatory lung injury when administered as rescue therapy in our canine model of LPS-induced ALI. This improvement is observed in the absence of changes in local pulmonary inflammatory cytokine production and an augmentation of systemic inflammation.

PMID:
19010292
PMCID:
PMC2605585
DOI:
10.1016/j.trsl.2008.09.002
[Indexed for MEDLINE]
Free PMC Article

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