Correlation between immune-related Tryptophan-Kynurenine pathway and severity of severe pneumonia and inflammation-related polyunsaturated fatty acids.

Abstract

BACKGROUND:

Immune dysfunction and oxidative stress caused by severe pneumonia can lead to multiple organ dysfunction and even death, causing a significant impact on health and the economy. Currently, great progress has been made in the diagnosis and treatment of this disease, but the mortality rate remains high (approximately 50%). Therefore, there is still potential for further exploration of the immune response mechanisms against severe pneumonia.

OBJECTIVE:

This study analyzed the difference in serum metabolic profiles between patients with severe pneumonia and health individuals through metabolomics, aiming to uncover the correlation between the Tryptophan-Kynurenine pathway and the severity of severe pneumonia, as well as N-3/N-6 polyunsaturated fatty acids (PUFAs).

METHODS:

In this study, 44 patients with severe pneumonia and 37 health controls were selected. According to the changes in the disease symptoms within the 7 days of admission, the patients were divided into aggravation (n = 22) and remission (n = 22) groups. Targeted metabolomics techniques were performed to quantify serum metabolites and analyze changes between groups.

RESULTS:

Metabolomics analysis showed that serum kynurenine and kynurenine/tryptophan (K/T) were significantly increased and tryptophan was significantly decreased in patients with severe pneumonia; HETE and HEPE in lipids increased significantly, while eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), α-linolenic acid (linolenic acid, α-LNA), arachidonic acid (ARA), Dihomo-γ-linolenic acid (DGLA), and 13(s)-hydroperoxylinoleic acid (HPODE) decreased significantly. Additionally, the longitudinal comparison revealed that Linolenic acid, DPA, and Tryptophan increased significantly in the remission group, while and kynurenine and K/T decreased significantly. In the aggravation group, Kynurenine and K/T increased significantly, while ARA, 8(S)-hydroxyeicosatetraenoic acid (HETE), 11(S)-HETE, and Tryptophan decreased significantly. The correlation analysis matrix demonstrated that Tryptophan was positively correlated with DGLA, 12(S)-hydroxyeicosapentaenoic acid (HEPE), ARA, EPA, α-LNA, DHA, and DPA. Kynurenine was positively correlated with 8(S)-HETE and negatively correlated with DHA. Additionally, K/T was negatively correlated with DGLA, ARA, EPA, α-LNA, DHA, and DPA.

CONCLUSION:

This study revealed that during severe pneumonia, the Tryptophan-Kynurenine pathway was activated and was positively correlated with the disease progression. On the other hand, the activation of the Tryptophan-Kynurenine pathway was negatively correlated with N-3/N-6 PUFAs.

• Authors: Baojun Guo, Mingshan Xue, Teng Zhang, Hui Gan, Runpei Lin, Mingtao Liu, Yuhong Liao, Jiali Lyu, Peiyan Zheng, Baoqing Sun
• Journal: Immunity, inflammation and disease (Immun Inflamm Dis) Vol. 11 Issue 11 Pg. e1088 (Nov 2023) ISSN: 2050-4527 [Electronic] England
• PMID: 38018595 (Publication Type: Journal Article)
• Copyright: © 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.

Chemical References

• Tryptophan
• Kynurenine
• Fatty Acids, Unsaturated
• Fatty Acids, Omega-3
• Arachidonic Acid
• Hydroxyeicosatetraenoic Acids
• Linolenic Acids

Topics

• Humans
• Tryptophan
• Kynurenine
• Fatty Acids, Unsaturated
• Fatty Acids, Omega-3
• Inflammation
• Arachidonic Acid (metabolism)
• Pneumonia (diagnosis)
• Hydroxyeicosatetraenoic Acids
• Linolenic Acids