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Type 1 reaction in leprosy patients corresponds with a decrease in pro-resolving and an increase in pro-inflammatory lipid mediators.

Abstract

BACKGROUND: Type 1 reaction (T1R) is an acute Th1 inflammatory episode in leprosy patients. While immunological responses associated with T1R have been investigated, the corresponding metabolic responses that could contribute to T1R pathology have received little attention.

METHODS: Metabolomics-based analyses of sera from T1R (n=7) and T1R-free (n=9) patients were conducted via liquid chromatography-mass spectrometry (LC-MS). Serum metabolites that significantly differed (p<0.05) with a log2 fold change of ≥1.0 between patient groups were interrogated against known metabolic pathways. The structural identification of targeted metabolites were confirmed and abundance changes validated by mass spectrometry and enzyme-linked immunoassay (EIA).

RESULTS: Forty metabolic pathways were perturbed in T1R patients, with 71 dysregulated metabolites mapping to pathways for lipid mediators of inflammation. Of note was an increase in the abundance of the pro-inflammatory leukotriene B4 (LTB4), and a corresponding decrease in pro-resolving resolvin D1 (RvD1). Also, levels of prostaglandin D2 (PGD2) and lipoxin A4 (LXA4) in T1R patients were significantly increased, while prostaglandin E2 (PGE2) was decreased.

CONCLUSIONS: The dysregulation of metabolic pathways leading to abundance shifts between pro-inflammatory and pro-resolving lipid mediators provides a link between metabolic and cellular immune responses that result in the Th1-mediated pathology of T1R.

More information

Type
Journal Article
Author
Silva C
Webb K
Andre BG
Marques MAM
Carvalho FM
Macedo CS
Pinheiro R
Sarno E
Pessolani M
Belisle JT