Omega-3 fatty acids enhance tumor necrosis factor-alpha levels in heart transplant recipients.
BACKGROUND
Proinflammatory cytokines may contribute to clinical complications in heart transplant (HTx) recipients. Previous studies have shown immunomodulating effects of omega-3 fatty acids, but the results are somewhat conflicting. In this study, we examined plasma levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL) 10, and their relations to antioxidant vitamins in 45 HTx recipients before and after treatment with omega-3 fatty acids or placebo.


METHODS
The patients were long-time survivors of heart transplantation, randomized in a double-blind fashion to receive omega-3 fatty acids (3.4 g/day) or placebo for 1 year. Plasma levels of cytokines were measured by enzyme immunoassays and vitamin A, vitamin E, and beta-carotene by high-performance liquid chromatography.


RESULTS
In the omega-3, but not in the placebo group, there was a rise in the proinflammatory cytokine TNF-alpha (P<0.05), a decrease in the anti-inflammatory cytokine IL-10 (P=0.07), and a rise in TNF/IL-10 ratio (P<0.05) after 12 months, suggesting a proinflammatory net effect. In the omega-3 group, the increase in TNF-alpha was associated with an increase in eicosapentaenoic acid in plasma (r=0.58, P<0.02). During omega-3 fatty-acid treatment, but not during placebo, there was a decrease in vitamin E (P<0.05) and beta-carotene (P<0.05) levels, and the decrease in vitamin E was inversely correlated with the increase in TNF-alpha (r= -0.56, P<0.01). The rise in TNF-alpha levels during omega-3 fatty acids treatment was most pronounced in those patients with transplant coronary artery disease (P<0.04).


CONCLUSIONS
Our data suggest that omega-3 fatty acids in HTx recipients may change the balance between proinflammatory and anti-inflammatory cytokines in an inflammatory direction, possibly related to prooxidative effects of these fatty acids.
Holm
T
T
Department of Cardiology, Research Institute for Internal Medicine, University of Oslo, Rikshospitalet, Norway. torbjorn.holm@klinmed.uio.no
Berge
R K
RK
Andreassen
A K
AK
Ueland
T
T
Kjekshus
J
J
Simonsen
S
S
Frøland
S
S
Gullestad
L
L
Aukrust
P
P
D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000097:blood; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000097:blood; D011182:Postoperative Care; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D014810:Vitamin E / Q000037:antagonists & inhibitors / Q000097:blood; D019207:beta Carotene / Q000037:antagonists & inhibitors / Q000097:blood
D015525:Fatty Acids, Omega-3; D018836:Inflammation Mediators; D010743:Phospholipids; D014409:Tumor Necrosis Factor-alpha; D019207:beta Carotene; D016753:Interleukin-10; D014810:Vitamin E