Docosahexaenoic and eicosapentaenoic acids inhibit in vitro human endothelial cell production of interleukin-6.
The interaction between lymphocytes, cytokines, and endothelial cells (EC) is a key step in the inflammatory process. Interleukin-6 (IL-6) a pleiotropic cytokine in its effects, seems to be an early indicator of acute systemic inflammation. In this study, we have examined the effects of polyunsaturated fatty acids (PUFAs) on the production of IL-6 by human unstimulated EC or EC stimulated with TNF-alpha (100 U/ml); IL-4 (100 U/ml); LPS (1 ug/ml); or allogeneic peripheral blood lymphocytes (PBL). Twenty-four hour culture supernatants of immunoreactive IL-6 were measured by Sandwich ELISA. We have shown that the production of IL-6 was potentiated when EC were stimulated with TNF-alpha; IL-4; LPS; or monocyte-depleted PBL in comparison to unstimulated EC. The addition of n-3 PUFAs in culture medium (100 ug/ml DHA or EPA) significantly reduces the production of IL-6 by unstimulated EC; or stimulated with TNF-alpha; IL-4 pg/ml); LPS or depleted PBL respectively for DHA and EPA, whereas the n-6 PUFAs (Arachidonic acid), even used at the highest concentration, was ineffective. This inhibitory effect is PUFA dose dependent but is more potent with EPA than DHA. Regardless of the mode of action, since IL-6 is known to be involved in hematopoiesis, in the regulation of the immune response and in the inflammatory reaction, these results suggest that n-3 PUFAs may play a role in suppressing inflammation. Further studies are needed to elucidate the mechanism involved and the choice between the two fatty acids for clinical and therapeutic purposes.
Khalfoun
B
B
Groupe Interactions Hote-Greffon Laboratoire D'Immunologie, Faculte De Medicine, Tours, France.
Thibault
F
F
Watier
H
H
Bardos
P
P
Lebranchu
Y
Y
D000328:Adult; D016718:Arachidonic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins
D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid