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Fenofibrate Facilitates Post-Active Tuberculosis Infection in Macrophages and is Associated with Higher Mortality in

Ching-Lung Liu1,2,3, Yen-Ta Lu1,2, I-Fan Tsai4

  • 1Division of Chest Medicine, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 104, Taiwan.

Journal of Clinical Medicine
|January 30, 2020
PubMed
Abstract

Insights

Long-term fenofibrate treatment in tuberculosis patients increases mortality risk. Fenofibrate also enhances Mycobacterium tuberculosis growth within macrophages, potentially by upregulating dormant genes.

Area of Science:

  • Infectious Diseases
  • Pharmacology
  • Microbiology

Background:

  • Mycobacterium tuberculosis (Mtb) is an intracellular pathogen residing within macrophages.
  • Tuberculosis (TB) treatment outcomes require further investigation, particularly concerning drug interactions.

Purpose of the Study:

  • To investigate the impact of long-term fenofibrate treatment on tuberculosis patients.
  • To assess the effect of fenofibrate on intracellular Mtb viability in human macrophages.

Main Methods:

  • Utilized epidemiological data from Taiwan's National Health Insurance Research Database for patient outcomes.
  • Conducted laboratory experiments assessing Mtb infection in fenofibrate-treated and untreated macrophages.
  • Examined Mtb growth, macrophage lipid accumulation, and gene expression.

Main Results:

  • Fenofibrate treatment correlated with increased mortality risk in TB patients over 11 years.
  • In vitro studies showed fenofibrate significantly increased Mtb bacilli count in macrophages.
  • Fenofibrate upregulated dormant Mtb genes (icl1, tgs1, devR) and showed an increasing trend in macrophage lipid content.

Conclusions:

  • Long-term fenofibrate use in TB patients is linked to higher mortality.
  • Mechanisms may involve fenofibrate-induced upregulation of Mtb lipid metabolism genes, enhanced intracellular Mtb growth, and persistence.
  • Fenofibrate may promote Mtb survival within a nutrient-rich macrophage environment.
Keywords:
fenofibratelipidmycobacterial tuberculosistuberculosis infection

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