Omega 3 (n−3) fatty acids down-regulate nuclear factor-kappa B (NF-κB) gene and blood cell adhesion molecule expression in patients with homozygous sickle cell disease

Abstract

Chronic inflammation and reduced blood levels of omega-3 fatty acids (n−3) are known characteristics of sickle cell disease (SCD).The anti-inflammatory properties of n−3 fatty acids are well recognized. Omega-3 treated (n = 24), hydroxyurea (HU) treated (n = 18), and n−3 untreated (n = 21) homozygous SCD patients (HbSS) and healthy (HbAA) controls (n = 25) matched for age (5-16 years), gender and socioeconomic status were studied. According to age (5-10) or (11-16) years, two or three capsules containing 277.8 mg docosahexaenoic (DHA) and 39.0 mg eicosapentaenoic (EPA) or high oleic acid placebo (41%) were assigned to n − 3 treated and n − 3 untreated groups, respectively. Hydroxyurea treated group was on dosage more than 20 mg/kg/day. The effect of supplementation on systemic and blood cell markers of inflammation was investigated. The n− 3 treated group had higher levels of DHA and EPA (p b 0.001) and lower white blood cell count and monocyte integrin (p b 0.05) compared with the n−3 untreated. No difference was detected between the two groups regarding C-reactive protein, granulocytes integrin and selectin, plasma tumour necrosis factor-α and interleukin-10. The n−3 treated group had lowered nuclear factor-kappa B (NF-κB) gene expression compared to n−3 untreated and HU treated groups (p b 0.05). This study provides evidence that supplementation with n− 3 fatty acids may ameliorate inflammation and blood cell adhesion in patients with SCD.

Pharmacotherapeutical strategies in the prevention of acute, vaso-occlusive pain in sickle cell disease: a systematic review

“…Interestingly, v-3 fatty acids are considered to be a multitarget intervention; in addition to having an antioxidative effect, they have been shown to inhibit platelet activation and blood-cell aggregation and inflammation and improve cell-membrane deformability. 65,[79][80][81][82] However, further confirmation of its efficacy on clinical outcomes is needed. The fact that 2 new phase 3 multicenter studies are expected to start enrollment soon therefore offers hope (registered at www.clinicaltrials.gov as #NCT02604368 and #NCT02525107).…”

The Role of Lipids in Inflammation: Review of the Evolving Pathogenesis of Sickle Cell Disease

“…This has been shown by several studies in past in different patient groups, including SC [6] and diabetes, [55] where they have been noted to induce amelioration of the symptoms and improve well-being [56]. Dietary DHA and EPA, after incorporation into the cell membrane, have also been shown in previous studies to increase membrane fluidity and thus affect the activity of the transmembrane proteins [12].…”

“…High levels of proinflammatory cytokines have been observed in these patients even while in steady state [42][43][44]. There's increasing evidence of the overexpression of the platelet selectin and its ligand (PSGL-1 or CD162), leukocyte selectin (CD62), β2 integrin and platelet endothelial cell adhesion molecule-1 [6]. The vascular endothelium is also activated with increased expression of inter-cellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1).…”

“…HU to a large extent also diminishes the cellular and endothelial adhesion molecules by reducing the total number of white cells available for adhesion [66]. Omega 3 fatty acids on the other hand suppress the expression of the adhesion molecules β2-integrin (CD-11b) and L-selectin (CD62L) in monocytes and granulocytes [6]. Intravenous gamma globulins as well as β3-integrin inhibitors are also being tested [63].…”

“…The mechanisms by which these poly-unsaturated fatty acids carry out these functions are not completely understood. However, recent studies have shown that intake of ω-3 fatty acids decreases levels of C reactive proteins (CRP), IL-6 and tumor necrosis factors (TNF-α) [6]. These actions are hypothesized to be effected mainly via regulations of the transcription factors; nuclear factor κ and peroxisome proliferator activated receptor.…”