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

• Published in: Nutrients 2020-09, Vol.12 (9), p.2897
• Main Authors: Nienaber, Arista, Baumgartner, Jeannine, Dolman, Robin C, Ozturk, Mumin, Zandberg, Lizelle, Hayford, Frank E A, Brombacher, Frank, Blaauw, Renee, Parihar, Suraj P, Smuts, Cornelius M, Malan, Linda
• Format: Article
• Language: English
• Subjects: Anemia - drug therapy; Anemia - microbiology; Animals; Cytokines - analysis; Cytokines - blood; Dietary Supplements; Docosahexaenoic Acids - administration & dosage; Eicosapentaenoic Acid - administration & dosage; Fatty Acids, Omega-3 - administration & dosage; Fatty Acids, Omega-3 - analysis; Fatty Acids, Omega-3 - blood; Inflammation - drug therapy; Inflammation - microbiology; Iron - administration & dosage; Lung - chemistry; Lung - microbiology; Lung - pathology; Male; Mice; Mice, Inbred C3H; Tuberculosis - complications; Tuberculosis - microbiology
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu12092897

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 -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.