A combination of LCPUFA ameliorates airway inflammation in asthmatic mice by promoting pro-resolving effects and reducing adverse effects of EPA.

Lipid mediators derived from omega (n)-3 and n-6 long-chain polyunsaturated fatty acids (LCPUFA) play key roles in bronchoconstriction, airway inflammation, and resolution processes in asthma. This study compared the effects of dietary supplementation with either a combination of LCPUFAs or eicosapentaenoic acid (EPA) alone to investigate whether the combination has superior beneficial effects on the outcome of asthmatic mice. Mice were sensitized with house dust mite (HDM) extract, and subsequently supplemented with either a combination of LCPUFAs or EPA alone in a recall asthma model. After the final HDM and LCPUFA administration, airway hyperresponsiveness (AHR), bronchoalveolar lavages, and lung histochemistry were examined. Lipid mediator profiles were determined by liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). The LCPUFA combination reduced AHR, eosinophilic inflammation, and inflammatory cytokines (IL-5, IFN-γ, and IL-6) in asthmatic mice, whereas EPA enhanced inflammation. The combination of LCPUFAs was more potent in downregulating EPA-derived LTB5 and LTC5 and in supporting DHA-derived RvD1 and RvD4 (2.22-fold and 2.58-fold higher levels) than EPA alone. Ex vivo experiments showed that LTB5 contributes to granulocytes' migration and M1-polarization in monocytes. Consequently, the LCPUFA combination ameliorated airway inflammation by inhibiting adverse effects of EPA and promoting pro-resolving effects supporting the lipid mediator-dependent resolution program.

A specific combined long-chain polyunsaturated fatty acid supplementation reverses fatty acid profile alterations in a mouse model of chronic asthma.

BACKGROUND: The immune-modulating potential of long-chain polyunsaturated fatty acids (LCPUFAs) based on their conversion into lipid mediators in inflammatory situations has been proven by several studies. Respecting the immune-modulative role of lipid mediators in bronchoconstriction, airway inflammation and resolution of inflammatory processes, LCPUFAs play an important role in asthma. To design a disease-specific and most beneficial LCPUFA supplementation strategy, it is essential to understand how asthma alters LCPUFA profiles. Therefore, this study characterizes the alterations of LCPUFA profiles induced by allergic asthma. In addition, this study explores whether a simple eicosapentaenoic acid (EPA) alone or a specific combined LCPUFA supplementation could restore imbalanced LCPUFA profiles. METHODS: Mice were sensitized with a daily dose of 40 µg house dust mite (HDM)-extract in a recall model and fed with either normal diet, EPA or a specific combined (sc)-LCPUFA supplementation containing EPA, docosahexaenoic acid (DHA), γ -linolenic acid (GLA) and stearidonic acid (SDA) for 24 days. After recall with HDM, mice were sacrificed and blood and lung tissue were collected. Fatty acid profiles were determined in plasma, blood cells and lung cells of asthmatic mice by capillary gas-chromatography. RESULTS: In lung cells of asthmatic mice, arachidonic acid (AA, p < 0.001) and DHA (p < 0.01) were increased while dihomo-γ-linolenic acid (DGLA, p < 0.05) was decreased. EPA supplementation increased only EPA (p < 0.001) and docosapentaenoic acid (DPA, p < 0.001), but neither DGLA nor DHA in lung cells of asthmatic mice. In contrast, a specific combined dietary supplementation containing n-3 and n-6 LCPUFAs could decrease AA (p < 0.001), increase EPA (p < 0.001), DPA (p < 0.001) and DHA (p < 0.01) and could reverse the lack of DGLA (p < 0.05). CONCLUSIONS: In summary, allergic asthma alters LCPUFA profiles in blood and lung tissue. In contrast to the EPA supplementation, the distinct combination of n-3 and n-6 LCPUFAs restored the LCPUFA profiles in lung tissue of asthmatic mice completely. Subsequently, sc-LCPUFA supplementation is likely to be highly supportive in limiting and resolving the inflammatory process in asthma.