Features of interaction between selective lipid metabolites and immune system signaling molecules in patients with asthma

Introduction. Lipid metabolism is a key component in many pathophysiological processes, and its disruption can play a significant role in the development of chronic inflammation in asthma. Aim. To determine the nature of the interaction between fatty acids (FAs) and their derivatives with cytokine parameters of the immune system and their contribution to systemic inflammation in patients with asthma. Materials and methods. The spectrum of FAs in the plasma of patients with asthma was analyzed using gas chromatography-mass spectrometry. Levels of endogenous fatty acid ethanolamides (NAEs) were measured using high-performance liquid chromatography with mass spectrometry. Cytokine levels were determined by enzyme-linked immunosorbent assay (ELISA). The degree of interaction between the parameters was assessed using systemic analysis based on the integral coupling index (D). Results. It was established that the immune system response was most strongly associated with the relative content of n-6 polyunsaturated fatty acids. Modification of the FA composition was most significantly linked with interleukins (IL) 17A, 10, 4, and 6. Endogenous NAEs—arachidonoylethanolamide (AEA, 20:4n6) and docosahexaenoylethanolamide (DHEA, 22:6n3)—showed significant involvement in cytokine regulation in mild asthma. NAE 20:4n6 had the strongest association with IL-17A, interferon-γ, tumor necrosis factor (TNF)-α, and IL-2; NAE 22:6n3 was associated with IL-17A, IL-6, and TNF-α. Conclusion. The study established the contribution of disturbances in trigger parameters of lipid metabolism to systemic inflammation. Modification of FA composition and disruption of the synthesis of their mediators lead to dysregulation of the cytokine network of the immune system, which may contribute to the development and chronicity of systemic inflammatory reactions in patients with asthma.

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