| First Author | Sager HB | Year | 2015 |
| Journal | Circulation | Volume | 132 |
| Issue | 20 | Pages | 1880-90 |
| PubMed ID | 26358260 | Mgi Jnum | J:239050 |
| Mgi Id | MGI:5824812 | Doi | 10.1161/CIRCULATIONAHA.115.016160 |
| Citation | Sager HB, et al. (2015) Targeting Interleukin-1beta Reduces Leukocyte Production After Acute Myocardial Infarction. Circulation 132(20):1880-90 |
| abstractText | 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. METHODS AND RESULTS: With the use of parabiosis surgery, this study shows that soluble danger signals, among them interleukin-1beta, increase bone marrow hematopoietic stem cell proliferation after MI. Data obtained in bone marrow reconstitution experiments reveal that interleukin-1beta 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-1beta suppresses these effects. Anti-interleukin-1beta 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. |
