Targeting Interleukin-1β Reduces Leukocyte Production After Acute Myocardial Infarction
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—Using parabiosis surgery, this study shows that soluble danger signals, among them interleukin-1 beta (IL-1β), increase bone marrow hematopoietic stem cell (HSC) proliferation after MI. Data obtained in bone marrow reconstitution experiments reveal that IL-1β enhances HSC proliferation by both direct actions on hematopoietic cells and through modulating the bone marrow's hematopoietic microenvironment. An antibody that neutralizes IL-1β suppresses these effects. Anti-IL-1β treatment dampens the post-MI increase in HSC 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.
- Received February 21, 2015.
- Revision received August 21, 2015.
- Accepted September 2, 2015.