DOCOSAHEXAENOIC AND EICOSAPENTAENOIC ACIDS INHIBIT IN-VITRO HUMAN LYMPHOCYTE-ENDOTHELIAL CELL-ADHESION

Dietary supplementation with fish oil, which contains high amounts of long chain omega 3 ((n-3)) polyunsaturated fatty acids (PUFAs), partic ularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has recently been shown to have protective and ameliorative effects on di seases characterized by chronic inflammatory reactions. Interactions b etween vascular endothelium, mononuclear cells, and cytokines are cruc ial steps in the course of inflammatory processes such as chronic graf t rejection. We therefore studied the effects of DHA and FPA on both t he adhesion of peripheral blood lymphocytes (PBL) to human endothelial cells (EC) in culture and the expression of EC-adhesion molecules and their counterreceptors on PBL. The addition of DHA or EPA to the adhe sion assay significantly decreased the adhesion of PBL to untreated EC and tumor necrosis factor-alpha (TNF alpha)-, interleukin (IL) 4-, an d lipopolysaccharide-stimulated EC. When EC were pretreated with (n-3) PUFAs for 18 hr, washed, and then stimulated by TNF alpha, IL-4, or l ipopolysaccharide, PBL adhesion was also significantly reduced compare d with controls. We also showed that PBL preincubated with DHA or EPA, and then washed and chromium radiolabeled, still exhibited an adhesio n inhibition to TNF alpha- and IL-4-treated EC as well as untreated EC . Cytofluorometry and immunoenzymatic analyses indicated that pretreat ment of EC with (n-3) PUFAs before their activation significantly redu ced the EC-induced expression of vascular cell adhesion molecule 1, wh ereas the level of expression of intercellular adhesion molecule 1 and E-selectin was not modified. Furthermore, we showed that incubation o f PBL with DHA or EPA moderately reduced the level of cell surface exp ression of L-selectin and leukocyte function-associated antigen 1, but not of very late antigen 4. In all cases, the inhibitory effect of (n -3) PUFAs was specific and dose dependent. In addition, DHA seems to b e a more potent inhibitor than EPA, but the two compounds in associati on had an additive effect. Regardless of the mode of action, this inhi bitory effect may explain the protective and ameliorative effects of ( n-3) PUFAs on diseases involving chronic inflammatory reaction.