Plasma LOX-Products and Monocyte Signaling Is Reduced by Adjunctive Cyclooxygenase-2 Inhibitor in a Phase I Clinical Trial of Tuberculosis Patients

Autor: Kristin Grotle Nore, Rasmus Mortensen, Emilie Layre, Kjetil Taskén, Jérôme Nigou, Hans Christian Dalsbotten Aass, Anne Ma Dyrhol-Riise, Dag Kvale, Kristian Tonby, Synne Jenum, Marthe Jøntvedt Jørgensen
Přispěvatelé: University of Oslo (UiO), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Rok vydání: 2021
Předmět:
0301 basic medicine
Microbiology (medical)
Tuberculosis
Lipoxygenase
Immunology
Inflammation
Pharmacology
[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Microbiology
Peripheral blood mononuclear cell
eicosanoids
03 medical and health sciences
Cellular and Infection Microbiology
0302 clinical medicine
cyclooxygenase-2 inhibitor
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Humans
Medicine
innate immunity
Original Research
Cyclooxygenase 2 Inhibitors
biology
business.industry
Monocyte
[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy
medicine.disease
QR1-502
cytokines
3. Good health
030104 developmental biology
Infectious Diseases
medicine.anatomical_structure
tuberculosis
Eicosanoid
030220 oncology & carcinogenesis
Leukocytes
Mononuclear
lipooxygenase
biology.protein
Cyclooxygenase
Antibody
medicine.symptom
monocytes
business
Etoricoxib
host-directed therapy (HDT)
medicine.drug
Zdroj: Frontiers in Cellular and Infection Microbiology
Frontiers in Cellular and Infection Microbiology, Frontiers, 2021, 11, pp.669623. ⟨10.3389/fcimb.2021.669623⟩
Frontiers in Cellular and Infection Microbiology, Vol 11 (2021)
ISSN: 2235-2988
Popis: IntroductionEicosanoids and intracellular signaling pathways are potential targets for host-directed therapy (HDT) in tuberculosis (TB). We have explored the effect of cyclooxygenase 2 inhibitor (COX-2i) treatment on eicosanoid levels and signaling pathways in monocytes.MethodsPeripheral blood mononuclear cells isolated from TB patients included in a randomized phase I clinical trial of standard TB treatment with (n=21) or without (n=18) adjunctive COX-2i (etoricoxib) were analyzed at baseline, day 14 and day 56. Plasma eicosanoids were analyzed by ELISA and liquid chromatography-mass spectrometry (LC-MS), plasma cytokines by multiplex, and monocyte signaling by phospho-flow with a defined set of phospho-specific antibodies.ResultsLipoxygenase (LOX)-derived products (LXA4 and 12-HETE) and pro-inflammatory cytokines were associated with TB disease severity and were reduced during TB therapy, possibly accelerated by adjunctive COX-2i. Phosphorylation of p38 MAPK, NFkB, Erk1/2, and Akt in monocytes as well as plasma levels of MIG/CXCL9 and procalcitonin were reduced in the COX-2i group compared to controls.ConclusionCOX-2i may reduce excess inflammation in TB via the LOX-pathway in addition to modulation of phosphorylation patterns in monocytes. Immunomodulatory effects of adjunctive COX-2i in TB should be further investigated before recommended for use as a HDT strategy.
Databáze: OpenAIRE
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