Immunomodulation by n-3- versus n-6-rich lipid emulsions in murine acute lung injury--role of platelet-activating factor receptor.
OBJECTIVE
Cytokines, platelet-activating factor (PAF), and eicosanoids control local and systemic inflammation. Conventional soybean oil-based lipid emulsions used for parenteral nutrition may aggravate the leukocyte inflammatory response or adhesion to the vessel wall. Fish oil-based lipid emulsions, in contrast, may exert an anti-inflammatory effect.


METHODS
We investigated the impact of lipid emulsions on leukocyte invasion, protein leakage, and cytokines in two murine models of acute inflammation.


METHODS
Research laboratory of a university hospital.


METHODS
Wild-type mice and PAF-receptor knockout mice.


METHODS
Mice received an infusion of normal saline, fish oil- or soybean oil-based lipid emulsions before lipopolysaccharide challenge.


RESULTS
Preinfusion with soybean oil resulted in increased leukocyte invasion, myeloperoxidase activity, and protein leakage and exaggerated release of tumor necrosis factor (TNF)-alpha as well as macrophage inflammatory protein (MIP)-2 into the alveolar space after intratracheal lipopolysaccharide challenge. In contrast, preinfusion with fish oil reduced leukocyte invasion, myeloperoxidase activity, protein leakage, and TNF-alpha as well as MIP-2 generation. Corresponding profiles were found in plasma following intraperitoneal lipopolysaccharide application: Soybean oil increased but fish oil decreased the TNF-alpha and MIP-2 formation. When PAF-receptor-deficient mice were challenged with lipopolysaccharide, leukocyte invasion, lung tissue myeloperoxidase, cytokine generation, and alveolar protein leakage corresponded to those observed in wild-type animals. Fish oil and soybean oil lost their diverging effects on leukocyte transmigration, myeloperoxidase activity, leakage response, and cytokine generation in these knockout mice. Similarly, the differential impact of both lipid emulsions on these lipopolysaccharide-provoked changes was suppressed after pretreating animals with a PAF-receptor antagonist.


CONCLUSIONS
Fish oil- vs. soybean oil-based lipid infusions exert anti- vs. proinflammatory effects in murine models of acute inflammation. The PAF/PAF-receptor-linked signaling appears to be a prerequisite for this differential profile.
Schaefer
Martina Barbara
MB
University of Giessen Lung Center (UGLC), Justus-Liebig-University of Giessen, Giessen, Germany.
Ott
Juliane
J
Mohr
Andrea
A
Bi
Ming Hua
MH
Grosz
Andrea
A
Weissmann
Norbert
N
Ishii
Satoshi
S
Grimminger
Friedrich
F
Seeger
Werner
W
Mayer
Konstantin
K
D000818:Animals; D054426:Chemokine CXCL2; D018925:Chemokines / Q000502:physiology*; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology* / Q000627:therapeutic use; D005395:Fish Oils / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000628:therapy*; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D012128:Respiratory Distress Syndrome / Q000628:therapy*; D013024:Soybean Oil / Q000494:pharmacology* / Q000627:therapeutic use
D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D005217:Fat Emulsions, Intravenous; D005395:Fish Oils; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D013024:Soybean Oil