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Published ahead of print on February 25, 2003, doi:10.1164/rccm.200207-674OC

Am. J. Respir. Crit. Care Med., Volume 167, Number 10, May 2003, 1321-1328

A more recent version of this article appeared on May 15, 2003
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Submitted on July 9, 2002
Accepted on February 23, 2003

Parenteral nutrition with fish oil modulates cytokine response in septic patients

Konstantin Mayer1*, Stephanie Gokorsch1, Christine Fegbeutel1, Katja Hattar1, Simone Rosseau2, Dieter Walmrath1, Werner Seeger1, and Friedrich Grimminger1

1 Internal Medicine, Justus Liebig University, Giessen, Germany, 2 Internal Medicine, Charite, Humboldt University, Berlin, Germany

* To whom correspondence should be addressed. E-mail: Konstantin.Mayer{at}innere.med.uni-giessen.de.

Infusion of fish oil-based (n-3) lipids may influence leukocyte function and plasma lipids in critical care patients. Twenty-one septic patients requiring parenteral nutrition were randomized to receive a n-3 lipid emulsion rich in eicosapentaenoic acid and docosahexaenoic acid or a conventional (n-6)lipid emulsion (index fatty acid: arachidonic acid) for five days. The impact on plasma free fatty acids, mononuclear leukocyte cytokine generation, and membrane fatty acid composition was examined. Cytokine synthesis by isolated mononuclear leukocyte was elicited by endotoxin. Before onset of lipid infusion therapy, plasma free fatty acid concentrations were greatly increased in septic patients, with arachidonic acid by far surpassing eicosapentaenoic acid and docosahexaenoic acid, a feature maintained during conventional lipid infusion. Within two days of fish oil infusion, free n-3 fatty acids increased, and the n-3/n-6 ratio was reversed, with rapid incorporation of n-3 fatty acids into mononuclear leukocyte membranes. Generation of pro-inflammatory cytokines by mononuclear leukocytes was markedly amplified during n-6 and suppressed during n-3 lipid application. After termination of lipid administration, free n-3 fatty acid concentrations and mononuclear leukocyte cytokine synthesis returned to pre-infusion values. Use of lipid infusions might allow to combine intravenous alimentation with differential impact on inflammatory events and immunological functions in septic patients.
Key words: monocyte, eicosapentaenoic acid, arachidonic acid, mononuclear leukocyte




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