Division of Clinical Chemistry and Biochemistry and Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Clin Nutr. 2023 Dec;42(12):2422-2433. doi: 10.1016/j.clnu.2023.10.016. Epub 2023 Oct 17.
Parenteral nutrition (PN) rich in n-6 and n-3 long-chain fatty acids is used in clinical practice for nourishing patients who are unable to receive adequate nutrition through their digestive systems. In this study, we compare the effect on inflammation of the commonly used lipid emulsions Omegaven (n-3-rich) and Intralipid (n-6-rich) in human peripheral blood mononuclear cells (PBMCs).
PBMCs were treated with different doses of n-3-rich Omegaven and n-6-rich Intralipid and the immune cells were characterized by flow cytometry.
We show that incubation of PBMCs with n-3-rich Omegaven leads to an increase in expression of CD1d and CD86 in CD14+monocytes. At the same time, an increased number of NKT cells expressing cytotoxic T cell antigen 4 is observed, suggesting immunological synapse formation. Both CD14+monocytes and NKT cells showed an increase in IL-10 production and a reduction in the pro-inflammatory cytokines IFN-γ, TNF-α, and IL-4, which led to an increase in the number of FOXP3+T regulatory cells. In addition, we show that n-3-rich Omegaven reduces the expression of TNFα, IFNγ and IL-4 in CD4+T and CD8+T cells independent of the presented interaction between CD14+monocytes and NKT cells. The described mechanism of n-3 rich lipid emulsions was confirmed in PBMCs from patients with inflammatory bowel disease but not in colorectal cancer patients which seem to lack the interaction between CD14+monocytes and NKT cells.
These results show a mechanism for the beneficial effect of the n-3-rich Omegaven in patients with inflammatory conditions but questions its use in patients with cancer. Hence, our results may assist in choosing the best lipid emulsion for patients who require PN.
富含 n-6 和 n-3 长链脂肪酸的肠外营养(PN)用于临床滋养无法通过消化系统获得足够营养的患者。在这项研究中,我们比较了临床上常用的富含 n-3 的欧米加万(n-3 丰富)和英脱利匹特(n-6 丰富)脂质乳剂对人外周血单个核细胞(PBMC)炎症的影响。
用不同剂量的 n-3 丰富的欧米加万和 n-6 丰富的英脱利匹特处理 PBMC,并通过流式细胞术对免疫细胞进行特征描述。
我们发现,用 n-3 丰富的欧米加万孵育 PBMC 会导致 CD14+单核细胞中 CD1d 和 CD86 的表达增加。同时,观察到表达细胞毒性 T 细胞抗原 4 的 NKT 细胞数量增加,表明免疫突触形成。CD14+单核细胞和 NKT 细胞均增加了 IL-10 的产生,减少了促炎细胞因子 IFN-γ、TNF-α 和 IL-4,从而导致 FOXP3+T 调节细胞数量增加。此外,我们还表明,n-3 丰富的欧米加万可减少 CD4+T 和 CD8+T 细胞中 TNFα、IFNγ 和 IL-4 的表达,而与 CD14+单核细胞和 NKT 细胞之间的相互作用无关。在炎症性肠病患者的 PBMC 中证实了富含 n-3 的脂质乳剂的这种作用机制,但在结直肠癌患者中似乎缺乏 CD14+单核细胞和 NKT 细胞之间的相互作用。
这些结果显示了富含 n-3 的欧米加万在炎症患者中有益作用的机制,但对其在癌症患者中的应用提出了质疑。因此,我们的研究结果可能有助于为需要 PN 的患者选择最佳的脂质乳剂。