Investigation of the role of interleukin-6 and hepcidin antimicrobial peptide in the development of anemia with age
Bryan J. McCranor,
Jacqueline M. Langdon,
Olivier D. Prince,
Laurette K. Femnou,
Alan E. Berger,
Chris Cheadle,
Curt I. Civin,
Airie Kim,
Seth Rivera,
Tomas Ganz,
Sophie Vaulont,
Qian-Li Xue,
Jeremy D. Walston,
Cindy N. Roy
Affiliations
Bryan J. McCranor
Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Jacqueline M. Langdon
Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Olivier D. Prince
Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Laurette K. Femnou
Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Alan E. Berger
Lowe Family Genomics Core, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Chris Cheadle
Lowe Family Genomics Core, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Curt I. Civin
Center for Stem Cell Biology and Regenerative Medicine and Departments of Pediatrics and Physiology, University of Maryland School of Medicine, Baltimore, MD, USA
Airie Kim
Departments of Medicine and Pathology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA
Seth Rivera
Departments of Medicine and Pathology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA
Tomas Ganz
Departments of Medicine and Pathology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA
Sophie Vaulont
Institut Cochin, Institut National de la Santé et de la Recherche Medicale U1016, Paris, France
Qian-Li Xue
Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD, USA;Center on Aging and Health, Johns Hopkins Medical Institutions, Baltimore, MD, USA
Jeremy D. Walston
Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD, USA;Center on Aging and Health, Johns Hopkins Medical Institutions, Baltimore, MD, USA
Cindy N. Roy
Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD, USA;Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Anemia is common in older adults and associated with adverse health outcomes in epidemiological studies. A thorough understanding of the complex pathophysiological mechanisms driving anemia in the elderly is lacking; but inflammation, iron restriction, and impaired erythroid maturation are thought to influence the phenotype. We hypothesized that interleukin-6 contributes to this anemia, given its pro-inflammatory activities, its ability to induce hepcidin antimicrobial peptide, and its negative impact on several tissues in older adults. We tested this hypothesis by comparing changes in indices of inflammation, iron metabolism and erythropoiesis in aged C57BL/6 mice to aged mice with targeted deletions of interleukin-6 or hepcidin antimicrobial peptide. Circulating neutrophil and monocyte numbers and inflammatory cytokines increased with age. Decline in hemoglobin concentration and red blood cell number indicated that C57BL/6, interleukin-6 knockout mice, and hepcidin antimicrobial peptide knockout mice all demonstrated impaired erythropoiesis by 24 months. However, the interleukin-6 knock out genotype and the hepcidin antimicrobial peptide knock out genotype resulted in improved erythropoiesis in aged mice. Increased erythropoietic activity in the spleen suggested that the erythroid compartment was stressed in aged C57BL/6 mice compared to aged interleukin-6 knockout mice. Our data suggest C57BL/6 mice are an appropriate mammalian model for the study of anemia with age. Furthermore, although interleukin-6 and hepcidin antimicrobial peptide are not required, they can participate in the development of anemia in aging mice, and could be targeted, pre-clinically, with existing interventions to determine the feasibility of such agents for the treatment of anemia in older adults.
