title: Targeting Interleukin-1β Reduces Leukocyte Production After Acute Myocardial Infarction.
abstract: BACKGROUND
  Myocardial infarction (MI) is an ischemic wound that recruits millions of leukocytes. MI-associated blood leukocytosis correlates inversely with patient survival, yet the signals driving heightened leukocyte production after MI remain incompletely understood.
  
  
  RESULTS
  With the use of parabiosis surgery, this study shows that soluble danger signals, among them interleukin-1β, increase bone marrow hematopoietic stem cell proliferation after MI. Data obtained in bone marrow reconstitution experiments reveal that interleukin-1β enhances hematopoietic stem cell proliferation by both direct actions on hematopoietic cells and through modulation of the bone marrow's hematopoietic microenvironment. An antibody that neutralizes interleukin-1β suppresses these effects. Anti-interleukin-1β treatment dampens the post-MI increase in hematopoietic stem cell proliferation. Consequently, decreased leukocyte numbers in the blood and infarct reduce inflammation and diminish post-MI heart failure in ApoE(-/-) mice with atherosclerosis.
  
  
  CONCLUSIONS
  The presented insight into post-MI bone marrow activation identifies a mechanistic target for muting inflammation in the ischemically damaged heart.
authors.affiliation: From Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston, MA (H.B.S., T.H., M.H., P.D., G.C., M.S., G.R.W., B.T., Y.I., Y.S., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
authors.forename: Hendrik B
authors.initials: HB
authors.lastname: Sager
authors.affiliation: From Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston, MA (H.B.S., T.H., M.H., P.D., G.C., M.S., G.R.W., B.T., Y.I., Y.S., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
authors.forename: Timo
authors.initials: T
authors.lastname: Heidt
authors.affiliation: From Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston, MA (H.B.S., T.H., M.H., P.D., G.C., M.S., G.R.W., B.T., Y.I., Y.S., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
authors.forename: Maarten
authors.initials: M
authors.lastname: Hulsmans
authors.affiliation: From Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston, MA (H.B.S., T.H., M.H., P.D., G.C., M.S., G.R.W., B.T., Y.I., Y.S., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
authors.forename: Partha
authors.initials: P
authors.lastname: Dutta
authors.affiliation: From Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston, MA (H.B.S., T.H., M.H., P.D., G.C., M.S., G.R.W., B.T., Y.I., Y.S., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
authors.forename: Gabriel
authors.initials: G
authors.lastname: Courties
authors.affiliation: From Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston, MA (H.B.S., T.H., M.H., P.D., G.C., M.S., G.R.W., B.T., Y.I., Y.S., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
authors.forename: Matthew
authors.initials: M
authors.lastname: Sebas
authors.affiliation: From Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston, MA (H.B.S., T.H., M.H., P.D., G.C., M.S., G.R.W., B.T., Y.I., Y.S., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Wojtkiewicz
authors.affiliation: From Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston, MA (H.B.S., T.H., M.H., P.D., G.C., M.S., G.R.W., B.T., Y.I., Y.S., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
authors.forename: Benoit
authors.initials: B
authors.lastname: Tricot
authors.affiliation: From Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston, MA (H.B.S., T.H., M.H., P.D., G.C., M.S., G.R.W., B.T., Y.I., Y.S., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Iwamoto
authors.affiliation: From Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston, MA (H.B.S., T.H., M.H., P.D., G.C., M.S., G.R.W., B.T., Y.I., Y.S., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: From Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston, MA (H.B.S., T.H., M.H., P.D., G.C., M.S., G.R.W., B.T., Y.I., Y.S., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.affiliation: From Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston, MA (H.B.S., T.H., M.H., P.D., G.C., M.S., G.R.W., B.T., Y.I., Y.S., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.affiliation: From Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston, MA (H.B.S., T.H., M.H., P.D., G.C., M.S., G.R.W., B.T., Y.I., Y.S., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
authors.forename: Filip K
authors.initials: FK
authors.lastname: Swirski
authors.affiliation: From Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston, MA (H.B.S., T.H., M.H., P.D., G.C., M.S., G.R.W., B.T., Y.I., Y.S., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.). mnahrendorf@mgh.harvard.edu.
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D053583:Interleukin-1beta; D011994:Recombinant Proteins
keywords: hematopoiesis; hematopoietic stem cells; interleukin-1β; myocardial infarction