title: Type 1 Reaction in Patients With Leprosy Corresponds to a Decrease in Proresolving Lipid Mediators and an Increase in Proinflammatory Lipid Mediators.
abstract: Type 1 reaction (T1R) is an acute T-helper type 1 (Th1) inflammatory episode in patients with leprosy. While immunological responses associated with T1R have been investigated, the corresponding metabolic responses that could contribute to T1R pathology have received little attention.
  
  
  
  Metabolomics-based analyses of sera from 7 patients with and 9 without T1R were conducted via liquid chromatography-mass spectrometry. Serum metabolites present at levels that significantly differed (P < .05) with a log2 fold change of ≥ 1.0 between patient groups were interrogated against known metabolic pathways. The structural identification of targeted metabolites was confirmed and abundance changes validated by mass spectrometry and enzyme-linked immunoassay.
  
  
  
  Forty metabolic pathways were perturbed in patients with T1R, with 71 dysregulated metabolites mapping to pathways for lipid mediators of inflammation. Of note was an increase in the abundance of the proinflammatory leukotriene B4 (LTB4) and a corresponding decrease in the level of proresolving resolvin D1 (RvD1). Also, levels of prostaglandin D2 (PGD2) and lipoxin A4 (LXA4) in patients with T1R were significantly increased, while the level of prostaglandin E2 (PGE2) was decreased.
  
  
  
  The dysregulation of metabolic pathways leading to abundance shifts between proinflammatory and proresolving lipid mediators provides a link between metabolic and cellular immune responses that result in the Th1-mediated pathology of T1R.
authors.affiliation: Mycobacteria Research Laboratories and.|Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins; and.
authors.forename: Carlos A M
authors.initials: CA
authors.lastname: Silva
authors.affiliation: Mycobacteria Research Laboratories and.|Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins; and.
authors.forename: Kristofor
authors.initials: K
authors.lastname: Webb
authors.affiliation: Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins; and.
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Andre
authors.affiliation: Mycobacteria Research Laboratories and.|Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins; and.|Cellular Microbiology Laboratory and.
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Marques
authors.affiliation: Cellular Microbiology Laboratory and.
authors.forename: Fernanda Marques
authors.initials: FM
authors.lastname: Carvalho
authors.affiliation: Cellular Microbiology Laboratory and.|Center for Technological Development in Health, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Cristiana Santos
authors.initials: CS
authors.lastname: de Macedo
authors.affiliation: Leprosy Laboratory, Oswaldo Cruz Institute, and.
authors.forename: Roberta Olmo
authors.initials: RO
authors.lastname: Pinheiro
authors.affiliation: Leprosy Laboratory, Oswaldo Cruz Institute, and.
authors.forename: Euzenir Nunes
authors.initials: EN
authors.lastname: Sarno
authors.affiliation: Cellular Microbiology Laboratory and.
authors.forename: Maria Cristina Vidal
authors.initials: MC
authors.lastname: Pessolani
authors.affiliation: Mycobacteria Research Laboratories and.|Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins; and.
authors.forename: John T
authors.initials: JT
authors.lastname: Belisle
mesh_terms: D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology; D002853:Chromatography, Liquid; D005231:Fatty Acids, Unsaturated / Q000276:immunology; D005260:Female; D006017:Glycolipids / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007918:Leprosy / Q000276:immunology* / Q000378:metabolism; D008055:Lipids / Q000276:immunology*; D008297:Male; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways; D055432:Metabolomics; D008875:Middle Aged; D009166:Mycobacterium leprae / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D005231:Fatty Acids, Unsaturated; D006017:Glycolipids; D018836:Inflammation Mediators; D008055:Lipids; C045169:phenolic glycolipid I, Mycobacterium leprae
keywords: Leprosy; lipid mediators; metabolomics; specialized proresolving mediators.; type 1 reaction