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Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in Mycobacterium tuberculosis -Infected Mice

Authors
  • Nienaber, Arista1
  • Baumgartner, Jeannine1, 2
  • Dolman, Robin C.1
  • Ozturk, Mumin3, 4
  • Zandberg, Lizelle1
  • Hayford, Frank E. A.1, 5
  • Brombacher, Frank3, 4, 6
  • Blaauw, Renee
  • Parihar, Suraj P.3, 4, 6, 7
  • Smuts, Cornelius M.1
  • Malan, Linda1
  • 1 (L.M.)
  • 2 Laboratory of Human Nutrition, ETH, 8092 Zurich, Switzerland
  • 3 (S.P.P.)
  • 4 Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology and South African Medical Research Council (SAMRC) Immunology of Infectious Diseases, University of Cape Town, Cape Town 7925, South Africa
  • 5 Department of Nutrition and Dietetics, School of biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, Accra Box KB143, Ghana
  • 6 Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa) and Institute of Infectious Diseases and Molecular Medicine (IDM), University of Cape Town, Cape Town 7925, South Africa
  • 7 Division of Medical Microbiology, Institute of Infectious Diseases and Molecular Medicine (IDM), Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
Type
Published Article
Journal
Nutrients
Publisher
MDPI AG
Publication Date
Sep 22, 2020
Volume
12
Issue
9
Identifiers
DOI: 10.3390/nu12092897
PMID: 32971969
PMCID: PMC7551947
Source
PubMed Central
Keywords
License
Green

Abstract

Progressive inflammation and anemia are common in tuberculosis (TB) and linked to poor clinical outcomes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have inflammation-resolving properties, whereas iron supplementation in TB may have limited efficacy and enhance bacterial growth. We investigated effects of iron and EPA/DHA supplementation, alone and in combination, on inflammation, anemia, iron status markers and clinical outcomes in Mycobacterium tuberculosis -infected C3HeB/FeJ mice. One week post-infection, mice received the AIN-93 diet without (control) or with supplemental iron (Fe), EPA/DHA, or Fe+EPA/DHA for 3 weeks. Mice supplemented with Fe or EPA/DHA had lower soluble transferrin receptor, ferritin and hepcidin than controls, but these effects were attenuated in Fe+EPA/DHA mice. EPA/DHA increased inflammation-resolving lipid mediators and lowered lung IL-1α, IFN-γ, plasma IL-1β, and TNF-α. Fe lowered lung IL-1α, IL-1β, plasma IL-1β, TNF-α, and IL-6. However, the cytokine-lowering effects in the lungs were attenuated with Fe+EPA/DHA. Mice supplemented with EPA/DHA had lower lung bacterial loads than controls, but this effect was attenuated in Fe+EPA/DHA mice. Thus, individually, post-infection EPA/DHA and iron supplementation lowered systemic and lung inflammation and mitigated anemia of infection in TB, but not when combined. EPA/DHA also enhanced bactericidal effects and could support inflammation resolution and management of anemia.

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