Macrophage migration inhibitory factor is a cardiac-derived myocardial depressant factor

Leslie B. Garner, Monte S. Willis, Deborah L. Carlson, J. Michael DiMaio, Michael D. White, D. Jean White, Glenn A. Adams IV, Jureta W. Horton, Brett P. Giroir

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Macrophage migration inhibitory factor (MIF) is a pluripotent proinflammatory cytokine that is ubiquitously expressed in organs, including the heart. However, no specific role for MIF in modulating cardiac performance has yet been described. Therefore, we examined cardiac MIF expression in mice after LPS challenge (4 mg/kg) and tested the hypothesis that MIF is a mediator of LPS-induced cardiac dysfunction. Western blots of whole heart lysates, as well as immunohistochemistry, documented constitutive MIF protein expression in the heart. Cardiac MIF protein levels significantly decreased after LPS challenge, reaching a nadir at 12 h, and then returned to baseline by 24 h. This pattern was consistent with MIF release from cytoplasmic stores after endotoxin challenge. After release of protein, MIF mRNA levels increased 24-48 h postchallenge. To determine the functional consequences of MIF release, we treated LPS-challenged mice with anti-MIF neutralizing antibodies or isotype control antibodies. Anti-MIF-treated animals had significantly improved cardiac function, as evidenced by a significant improvement in left ventricular (LV) fractional shortening percentage at 8, 12, 24, and 48 h after endotoxin challenge. In support of these findings, perfusion of isolated beating mouse hearts (Langendorff preparation) with recombinant MIF (20 ng/ml) led to a significant decrease in both systolic and diastolic performance [LV pressure (LVP), positive and negative first derivative of LVP with respect to time, and rate of LVP rise at developed pressure of 40 mmHg]. This study demonstrates that MIF mediates LPS-induced cardiac dysfunction and suggests that MIF should be considered a pharmacological target for the treatment of cardiac dysfunction in sepsis and potentially other cardiac diseases.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number6 54-6
StatePublished - Dec 2003

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Myocardial Depressant Factor
Macrophage Migration-Inhibitory Factors
Pressure
Endotoxins
Proteins
Ventricular Pressure
Neutralizing Antibodies
Heart Diseases
Sepsis
Perfusion
Western Blotting
Immunohistochemistry
Pharmacology
Cytokines
Messenger RNA
Antibodies

Keywords

  • Cardiac dysfunction
  • Innate immunity
  • Lipopolysaccharide
  • Sepsis

ASJC Scopus subject areas

  • Physiology

Cite this

Macrophage migration inhibitory factor is a cardiac-derived myocardial depressant factor. / Garner, Leslie B.; Willis, Monte S.; Carlson, Deborah L.; DiMaio, J. Michael; White, Michael D.; White, D. Jean; Adams IV, Glenn A.; Horton, Jureta W.; Giroir, Brett P.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 285, No. 6 54-6, 12.2003.

Research output: Contribution to journalArticle

Garner, LB, Willis, MS, Carlson, DL, DiMaio, JM, White, MD, White, DJ, Adams IV, GA, Horton, JW & Giroir, BP 2003, 'Macrophage migration inhibitory factor is a cardiac-derived myocardial depressant factor', American Journal of Physiology - Heart and Circulatory Physiology, vol. 285, no. 6 54-6.
Garner, Leslie B. ; Willis, Monte S. ; Carlson, Deborah L. ; DiMaio, J. Michael ; White, Michael D. ; White, D. Jean ; Adams IV, Glenn A. ; Horton, Jureta W. ; Giroir, Brett P. / Macrophage migration inhibitory factor is a cardiac-derived myocardial depressant factor. In: American Journal of Physiology - Heart and Circulatory Physiology. 2003 ; Vol. 285, No. 6 54-6.
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