Resolution of inflammation and sepsis survival are improved by dietary Ω-3 fatty acids

Abstract

Critical conditions such as sepsis following infection or traumatic injury disturb the complex state of homeostasis that may lead to uncontrolled inflammation resulting in organ failure, shock and death. They are associated with endogenous mediators that control the onset of acute inflammatory response, but the central problem remains the complete resolution of inflammation. Omega-3 enriched lipid emulsions (Ω-3+ LEs) were used in experimental studies and clinical trials to establish homeostasis, yet with little understanding about their role on the resolution of inflammation and tissue regeneration. Here, we demonstrate that Ω-3 lipid emulsions (LEs) orchestrate inflammation-resolution/regeneration mechanism during sterile peritonitis and murine polymicrobial sepsis. Ω-3+ LEs recessed neutrophil infiltration, reduced pro-inflammatory mediators, reduced the classical monocyte and enhanced the non-classical monocytes/macrophages recruitment and finally increased the efferocytosis in sepsis. The actions of Ω-3+ LE were 5-lipoxygenase (5-LOX) and 12/15-lipoxygenase (12/15-LOX) dependent. Ω-3+ LEs shortened the resolution interval by 56%, stimulated the endogenous biosynthesis of resolution mediators lipoxin A4, protectin DX and maresin 1 and contributed to tissue regeneration. Ω-3+ LEs protected against hypothermia and weight loss and enhanced survival in murine polymicrobial sepsis. We highlighted a role of Ω-3+ LEs in regulating key mechanisms within the resolution terrain during murine sepsis. This might form the basis for a rational design of sepsis specific clinical nutrition.

Eicosanoid biosynthesis influences the virulence of Candida parapsilosis

“…In order to propose a possible structure for the obtained signal we carried out tandem mass spectrometry as well as MS 3 analysis of the obtained peak. As can be seen from Figure 3, based on the mass spectrometric data, we propose the observed oxylipin to be a 5-D2-IsoP [23]. The fragment m/z 115 is indicative of a 5-hydroxy group, in combination with the MS/MS fragments m/z 217 and 271 as well as the MS 3 fragments m/z 215 and 106 we propose 5-D2-IsoP to be a likely candidate molecule for the observed signal.…”

The Influence of Dietary Fatty Acids on Immune Responses

“…The protective effect of PUFAs is also observed in uninfected mice, fed with HFD-P, shown as a higher frequency of neutrophils in the bone marrow and on the site of ongoing inflammation [115]. The anti-inflammatory effects of PUFAs in the course of bacterial infection depend on the diet rich in n-3 PUFAs [158,159]. On the other hand, n-3 PUFAs can also boost proinflammatory responses in neutrophils, as shown in mice genetically susceptible to colitis [121].…”

Novel mediators and mechanisms in the resolution of infectious inflammation: evidence for vagus regulation

“…The double lipoxygenase product 10,17-diHDHA denoted PDX is obtained via sequential steps of lipoxygenation to yield 10S,17S-diHDHA [33]. This PDX is an isomer of PD1 and has several actions on its own [60][61][62][63][64]. When PD1 is produced in neural systems, it is coined neuroprotectin D1 (NPD1), with protective actions demonstrated in retina, brain and pain [65][66][67].…”