Modulation of Cytokine Production In Vivo by Dietary Essential Fatty Acids in Patients with Colorectal Cancer

Abstract

1. The effects of essential fatty acids (gamma-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid), at a dose of 4.8 g/day, given in combination as dietary supplements, on cytokine production were investigated in patients with colorectal cancer. 2. Total serum cytokines--interleukin (interleukin-1 beta, 2, 4 and 6), tumour necrosis factor-alpha and interferon-gamma--were analysed using the enzyme-linked immunosorbent assay technique at different time intervals during the course of essential fatty acid supplementation. 3. Fatty acid uptake and patient compliance were confirmed by a significant increase in serum levels of gamma-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid in all three fractions: tricylglycerol, cholesterol and phospholipid. 4. There was no significant alteration in total serum cytokine concentration/levels in the first 2 months of essential fatty acid ingestion, but the levels of serum cytokines steadily declined thereafter, reaching minimum levels after 6 months of essential fatty acid supplementation. 5. Essential fatty acids, at the dose and duration (6 months) used in this study, reduced total serum interleukin-1 beta levels by 61% (P = 0.044), interleukin-2 by 63% (P = 0.05), interleukin-4 by 69% (P = 0.025), interleukin-6 by 83% (P = 0.030), tumour necrosis factor-alpha by 73% (P = 0.040) and interferon-gamma by 67% (P = 0.050). 6. Three months after cessation of essential fatty acid intake, however, these cytokine levels returned to presupplementation values. 7. This present study has shown that long-term n-3 and n-6 EFA ingestion results in a significant reduction in circulating key cytokines. The precise mechanism of this reduction is unclear.

Neuroprotective Effect of Eicosapentaenoic Acid in Hippocampus of Rats Exposed to γ-Irradiation

“…There are multiple possible ways in which EPA may act, some of them being related to its known anti-inflammatory actions (30,31). At the molecular level, the effect might be related to inhibition of phospholipases such as phospholipase A 2 (45), inhibition of cyclooxygenases and lipoxygenases (46), reduction of pro-inflammatory cytokine synthesis (47,48), activation of PPAR receptors (49 -51), or inhibition of transcription factor synthesis (52). In addition to this, radiation damages membranes by destroying their polyunsaturated fatty acid components, and the EPA may act in part by providing a substrate for membrane repair (53).…”

Interaction between Nutrients, Pro-Inflammatory Cytokines and Inflammation

“…This may partly explain the anti-inflammatory effects of fish oil. y-Linolenic acid also has a suppressive effect on plasma concentrations of a wide range of cytokines (IL-1, IL-2, IL-4, IL-6, TNF-(r and y-interferon) in patients with colorectal cancer [64]. Fish oil also confers protection in animals against the lethal effects of endotoxin, burn injury and bacterial infection [65-681. An increasing body of evidence suggests that aberrant cytokine production is involved in atherosclerosis [39].…”

Docosahexaenoic Acid Ameliorates Murine Ischemic Acute Renal Failure and Prevents Increases in mRNA Abundance for both TNF-α and Inducible Nitric Oxide Synthase

“…Long-term dietary supplementation with DHA or DHA-containing fish oils (17)(18)(19)(20)(21)(22)(23) decreases TNF-␣ production. Such diets also ameliorate ischemic ARF in dogs (24).…”