ACCUMULATION OF MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) AND HIGH MOBILITY GROUP BOX CHROMOSOMAL PROTEIN-1 (HMGB-1) IN THE LUNG DURING SEPSIS; IMPLICATIONS FOR CARDIAC FUNCTION.

Sepsis can cause myocardial dysfunction, which contributes to the high mortality of sepsis. Hypertonic saline (HS) has been reported to increase myocardial contractility in sepsis. In the present study, mechanisms of action of HS resuscitation (4 mL of 7.5% NaCl per kilogram) on cardiac function have been evaluated in septic rats. HS was administered 1 h after LPS (10 mg/kg, i.v.) challenge. The mean arterial blood pressure significantly decreased 4 h after LPS challenge, and septic shock was observed at the end of experiment (6 h). Posttreatment with HS prevented hypotension caused by LPS and significantly improved cardiac function, evidenced by increases in left ventricular developed pressure, mean+dP/dtand-dP/dt. The amplitude of electrical-stimulated intracellular Ca2+transient in isolated single cardiomyocytes was significantly reduced after 6 h LPS insult, which was recovered by HS. In addition, LPS resulted in significant increases in neutrophil myeloperoxidase activity, macrophage migration inhibitory factor (MIF), and NF-κB phospho-p65 protein levels in myocardium at 6 h, which were significantly attenuated by HS. In conclusion, HS improved myocardial contractility and prevented circulatory failure induced by endotoxemia, which may attribute to improvement of intracellular calcium handling process and inhibitory effects on neutrophil infiltration and MIF production in hearts.

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Correlation between Plasma Macrophage Migration Inhibitory Factor Levels and Long-Term Prognosis in Patients with Acute Myocardial Infarction Complicated with Diabetes

Mediators of Inflammation ◽

10.1155/2019/8276180 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Haiyi Yu ◽

Xinyu Wang ◽

Xiangning Deng ◽

Youyi Zhang ◽

Wei Gao

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Migration Inhibitory Factor ◽

Macrophage Migration Inhibitory Factor ◽

Left Ventricular ◽

Inhibitory Factor ◽

Macrophage Migration ◽

Long Term Prognosis

Macrophage migration inhibitory factor (MIF), a widely expressed pleiotropic cytokine, is reportedly involved in several cardiovascular diseases, in addition to inflammatory diseases. Plasma MIF levels are elevated in the early phase of acute cardiac infarction. This study is aimed at investigating the correlation between plasma MIF levels and cardiac function and prognosis in patients with acute ST-segment elevation myocardial infarction (STEMI) with or without diabetes mellitus. Overall, 204 patients with STEMI who underwent emergency percutaneous coronary intervention were enrolled: 57 and 147 patients in the diabetes and nondiabetes STEMI groups, respectively. Sixty-five healthy people were selected as controls. Plasma MIF levels were measured at the time of diagnosis. Basic clinical data and echocardiographic findings within 72 h of admission were collected. Patients were followed up, and echocardiograms were reviewed at the 12-month follow-up. Plasma MIF levels were significantly higher in the diabetes and nondiabetes STEMI groups than in the control group and in patients with Killip grade≥II STEMI than in those with Killip grade I. Plasma MIF levels were negatively correlated with the left ventricular ejection fraction (LVEF) of myocardial infarction in patients with or without diabetes in the acute phase of infarction, whereas the left ventricular diastolic dysfunction (LVDD) was positively correlated. MIF levels in the nondiabetes STEMI group were positively correlated with N-terminal pro-b-type natriuretic peptide levels and were associated with LVEF and LVDD at the 12-month follow-up. The risk of adverse cardiovascular and cerebrovascular events was significantly higher in the MIF high-level group (≥52.7 ng/mL) than in the nondiabetes STEMI group 36 months after presentation. Thus, MIF levels in STEMI patients with or without diabetes can reflect acute cardiac function. In STEMI patients without diabetes, MIF levels can also indicate cardiac function and long-term prognosis at the 12-month follow-up.

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Intravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain

PLoS ONE ◽

10.1371/journal.pone.0255975 ◽

2021 ◽

Vol 16 (8) ◽

pp. e0255975

Author(s):

Shaojing Ye ◽

Fei Ma ◽

Dlovan F. D. Mahmood ◽

Katherine L. Meyer-Siegler ◽

Raymond E. Menard ◽

...

Keyword(s):

Migration Inhibitory Factor ◽

Macrophage Migration Inhibitory Factor ◽

High Mobility ◽

Inhibitory Factor ◽

Macrophage Migration ◽

Urothelial Cells ◽

Bladder Pain ◽

Pre Treatment

Background Activation of intravesical protease activated receptor 4 (PAR4) leads to release of urothelial macrophage migration inhibitory factor (MIF). MIF then binds to urothelial MIF receptors to release urothelial high mobility group box-1 (HMGB1) and elicit bladder hyperalgesia. Since MIF binds to multiple receptors, we investigated the contribution of individual urothelial MIF receptors to PAR4-induced HMGB1 release in vivo and in vitro and bladder pain in vivo. Methodology/Principal findings We tested the effect of intravesical pre-treatment with individual MIF or MIF receptor (CD74, CXCR4, CXCR2) antagonists on PAR4-induced HMGB1 release in vivo (female C57/BL6 mice) and in vitro (primary human urothelial cells) and on PAR4-induced bladder hyperalgesia in vivo (mice). In mice, PAR4 induced HMGB1 release and bladder hyperalgesia through activation of intravesical MIF receptors, CD74 and CXCR4. CXCR2 was not involved in these effects. In primary urothelial cells, PAR4-induced HMGB1 release through activation of CD74 receptors. Micturition parameters in mice were not changed by any of the treatments. Conclusions/Significance Urothelial MIF receptors CD74 and CXCR4 mediate bladder pain through release of urothelial HMGB1. This mechanism may set up persistent pain loops in the bladder and warrants further investigation. Urothelial CD74 and CXCR4 may provide novel targets for interrupting bladder pain.

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MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) BLOCKADE IMPROVES CARDIAC FUNCTION AND SURVIVAL IN SEPSIS

Shock ◽

10.1097/00024382-200606001-00215 ◽

2006 ◽

Vol 25 (Supplement 1) ◽

pp. 71

Author(s):

E. Miller ◽

X Lin ◽

T. Sakuragi ◽

C. Metz ◽

K. Ojamaa ◽

...

Keyword(s):

Cardiac Function ◽

Migration Inhibitory Factor ◽

Macrophage Migration Inhibitory Factor ◽

Inhibitory Factor ◽

Macrophage Migration

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Macrophage migration inhibitory factor mediates late cardiac dysfunction after burn injury

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00189.2004 ◽

2005 ◽

Vol 288 (2) ◽

pp. H795-H804 ◽

Cited By ~ 33

Author(s):

Monte S. Willis ◽

Deborah L. Carlson ◽

J. Michael DiMaio ◽

Michael D. White ◽

D. Jean White ◽

...

Keyword(s):

Cardiac Function ◽

Migration Inhibitory Factor ◽

Cardiac Dysfunction ◽

Macrophage Migration Inhibitory Factor ◽

Burn Injury ◽

Total Body Surface Area ◽

Left Ventricular ◽

Inhibitory Factor ◽

Macrophage Migration ◽

Endotoxin Challenge

We have recently demonstrated that macrophage migration inhibitory factor (MIF) is a myocardial depressant protein and that MIF mediates late, prolonged cardiac dysfunction after endotoxin challenge in mice. Because many factors, including endotoxin, have been implicated in the pathogenesis of cardiac dysfunction after burn injury, we tested the hypothesis that MIF might also be the mediator of prolonged cardiac dysfunction in this model. At 4 h after 40% total body surface area burn in anesthetized mice, serum MIF levels increased significantly compared with baseline (2.2-fold). This increase was accompanied by a significant decrease in cardiac tissue MIF levels (2.1-fold decrease compared with controls). This pattern was consistent with MIF release from preformed cytoplasmic stores in the heart and other organs. To determine whether MIF mediates cardiac dysfunction after burn injury, mice were pretreated with anti-MIF neutralizing monoclonal antibodies or isotype control antibodies. Beginning 4 h after burn injury (and continuing through 48 h), burned mice demonstrated a significantly depressed left ventricular shortening fraction of 38.6 ± 1.8%, compared with the normal controls (56.0 ± 2.6%). Mice treated with anti-MIF displayed an initial depression of cardiac function similar to nontreated animals but then showed rapid restoration of cardiac function with complete recovery by 24 h, which persisted for the duration of the protocol. This study is the first to demonstrate that MIF mediates late, prolonged cardiac dysfunction after burn injury and suggests that MIF blockade should be considered a therapeutic target for the treatment of burn injury.

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