Skip to main content
SpringerLink
Log in

Macrophage Migration Inhibitory Factor in Critical Illness: Dr. Jekyll and Mr. Hyde?

  • Chapter
Annual Update in Intensive Care and Emergency Medicine 2013

Part of the book series: Annual Update in Intensive Care and Emergency Medicine ((AUICEM))

  • 2698 Accesses

Abstract

In critically ill patients, sepsis and its sequelae belong to the leading causes of death world-wide. During the last decades, the incidence of sepsis has been constantly increasing [1, 2]. Apart from the administration of antibiotics, treatment of sepsis still comprises mainly supportive strategies (including fluid resuscitation and administration of vasopressors). Several promising pharmacotherapeutic approaches failed to show beneficial effects, such as the inhibition of tumor necrosis factor (TNF)-α, the modulation of relative adrenal insufficiency and the administration of activated protein C [3–5].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Vincent JL, Sakr Y, Sprung CL et al (2006) Sepsis in European intensive care units: results of the SOAP study. Crit Care Med 34:344–353

    Article  PubMed  Google Scholar 

  2. Martin GS, Mannino DM, Eaton S, Moss M (2003) The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 348:1546–1554

    Article  PubMed  Google Scholar 

  3. Abraham E (1999) Why immunomodulatory therapies have not worked in sepsis. Intensive Care Med 25:556–566

    Article  PubMed  CAS  Google Scholar 

  4. Sprung CL, Annane D, Keh D et al (2008) Hydrocortisone therapy for patients with septic shock. N Engl J Med 358:111–124

    Article  PubMed  CAS  Google Scholar 

  5. Ranieri VM, Thompson BT, Barie PS et al (2012) Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 366:2055–2064

    Article  PubMed  CAS  Google Scholar 

  6. Calandra T, Echtenacher B, Roy DL et al (2000) Protection from septic shock by neutralization of macrophage migration inhibitory factor. Nature Med 6:164–170

    Article  PubMed  CAS  Google Scholar 

  7. Al-Abed Y, Dabideen D, Aljabari B et al (2005) ISO-1 binding to the tautomerase active site of MIF inhibits its pro-inflammatory activity and increases survival in severe sepsis. J Biol Chem 280:36541–36544

    Article  PubMed  CAS  Google Scholar 

  8. Stoppe C, Grieb G, Rossaint R et al (2012) High postoperative blood levels of macrophage migration inhibitory factor are associated with less organ dysfunction in patients after cardiac surgery. Mol Med 18:843–850

    Article  PubMed  CAS  Google Scholar 

  9. Miller EJ, Li J, Leng L et al (2008) Macrophage migration inhibitory factor stimulates AMP-activated proteinkinase in the ischaemic heart. Nature 451:578–582

    Article  PubMed  CAS  Google Scholar 

  10. Qi D, Hu X, Wu X, Merk M, Leng L, Bucala R, Young LH (2009) Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia/reperfusion. J Clin Invest 119:3807–3816

    Article  PubMed  CAS  Google Scholar 

  11. Koga K, Kenessey A, Powell SR, Sison CP, Miller EJ, Ojamaa K (2010) Macrophage migration inhibitory factor provides cardioprotection during ischemia/reperfusion by reducing oxidative stress. Antioxid Redox Signal 14:1191–1202

    Article  Google Scholar 

  12. Janeway Jr CA, Medzhitov R (2002) Innate immune recognition. Ann Rev Immunol 20:197–216

    Article  CAS  Google Scholar 

  13. Calandra T, Roger T (2003) Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol 3:791–800

    Article  PubMed  CAS  Google Scholar 

  14. Calandra T, Bochud PY, Heumann D (2002) Cytokines in septic shock. Curr Clin Top Infect Dis 22:1–23

    PubMed  Google Scholar 

  15. David JR (1966) Delayed hypersensitivity in vitro: its mediation by cell-free substances formed by lymphoid cell-antigen interaction. Proc Natl Acad Sci USA 56:72–77

    Article  PubMed  CAS  Google Scholar 

  16. Bernhagen J, Calandra T, Mitchell RA et al (1993) MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. Nature 365:756–759

    Article  PubMed  CAS  Google Scholar 

  17. Calandra T, Bernhagen J, Metz CN et al (1995) MIF as a glucocorticoid-induced modulator of cytokine production. Nature 377:68–71

    Article  PubMed  CAS  Google Scholar 

  18. Leng L, Metz CN, Fang Y et al (2003) MIF signal transduction initiated by binding to CD74. J Exp Med 197:1467–1476

    Article  PubMed  CAS  Google Scholar 

  19. Bernhagen J, Krohn R, Lue H et al (2007) MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment. Nat Med 13:587–596

    Article  PubMed  CAS  Google Scholar 

  20. Calandra T, Bernhagen J, Mitchell RA, Bucala R (1994) The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor. J Exp Med 179:1895–1902

    Article  PubMed  CAS  Google Scholar 

  21. Bozza FA, Gomes RN, Japiassu AM et al (2003) Macrophage migration inhibitory factor levels correlate with fatal outcome in sepsis. Shock 22:309–313

    Article  Google Scholar 

  22. Donnelly SC, Haslett C, Reid PT et al (1997) Regulatory role for macrophage migration inhibitory factor in acute respiratory distress syndrome. Nat Med 3:320–323

    Article  PubMed  CAS  Google Scholar 

  23. Onodera S, Kaneda K, Mizue Y, Koyama Y, Fujinaga M, Nishihira J (2000) Macrophage migration inhibitory factor up-regulates expression of matrix metalloproteinases in synovial fibroblasts of rheumatoid arthritis. J Biol Chem 275:444–450

    Article  PubMed  CAS  Google Scholar 

  24. Mitchell RA, Liao H, Chesney J et al (2002) Macrophage migration inhibitory factor (MIF) sustains macrophage proinflammatory function by inhibiting p53: regulatory role in the innate immune response. Proc Natl Acad Sci USA 99:345–350

    Article  PubMed  CAS  Google Scholar 

  25. Fingerle-Rowson G, Koch P, Bikoff R et al (2003) Regulation of macrophage migration inhibitory factor expression by glucocorticoids in vivo. Am J Pathol 162:47–56

    Article  PubMed  CAS  Google Scholar 

  26. Roger T, David J, Glauser MP, Calandra T (2001) MIF regulates innate immune responses through modulation of Toll-like receptor 4. Nature 414:920–924

    Article  PubMed  CAS  Google Scholar 

  27. Mitchell RA, Metz CN, Peng T, Bucala R (1999) Sustained mitogen-activated protein kinase (MAPK) and cytoplasmic phopholipase A2 activation by macrophage migration inhibitory factor (MIF). J Biol Chem 274:18100–18106

    Article  PubMed  CAS  Google Scholar 

  28. Lue H, Dewor M, Leng L, Bucala R, Bernhagen J (2011) Activation of the JNK signalling pathway by macrophage migration inhibitory factor (MIF) and dependence on CXCR4 and CD74. Cell Signal 23:135–144

    Article  PubMed  CAS  Google Scholar 

  29. Petrovsky N, Socha L, Silva D, Grossman AB, Metz C, Bucala R (2003) Macrophage migration inhibitory factor exhibits a pronounced circadian rhythm relevant to its role as a glucocorticoid counter-regulator. Immunol Cell Biol 81:137–143

    Article  PubMed  CAS  Google Scholar 

  30. Beishuizen A, Thijs LG, Haanen C, Vermes I (2001) Macrophage migration inhibitory factor and hypothalamo-pituitary-adrenal function during critical illness. J Clin Endocrinol Metab 86:2811–2816

    Article  PubMed  CAS  Google Scholar 

  31. Gando S, Sawamura A, Hayakawa M, Hoshino H, Kubota N, Nishihira J (2007) High macrophage migration inhibitory factor levels in disseminated intravascular coagulation patients with systemic inflammation. Inflammation 30:118–124

    Article  PubMed  CAS  Google Scholar 

  32. Thiele M, Bernhagen J (2005) Link between macrophage migration inhibitory factor and cellular redox regulation. Antioxid Redox Signal 7:1234–1248

    Article  PubMed  CAS  Google Scholar 

  33. Leaver SK, Maccallum NS, Pingle V et al (2010) Increased plasma thioredoxin levels in patients with sepsis: positive association with macrophage migration inhibitory factor. Intensive Care Med 36:336–341

    Article  PubMed  CAS  Google Scholar 

  34. Sprong T, Pickkers P, Geurts-Moespot A et al (2007) Macrophage migration inhibitory factor (MIF) in meningococcal septic shock and experimental human endotoxemia. Shock 27:482–487

    Article  PubMed  CAS  Google Scholar 

  35. Østergaard C, Benfield T (2009) Macrophage migration inhibitory factor in cerebrospinal fluid from patients with central nervous system infection. Crit Care 13:R101

    Article  PubMed  Google Scholar 

  36. Renner P, Roger T, Bochud PY et al (2012) A functional microsatellite of the macrophage migration inhibitory factor gene associated with meningococcal disease. FASEB J 26:907–916

    Article  PubMed  CAS  Google Scholar 

  37. Rahman SH, Menon KV, Holmfield JH, McMahon MJ, Guillou JP (2007) Serum macrophage migration inhibitory factor is an early marker of pancreatic necrosis in acute pancreatitis. Ann Surg 245:282–289

    Article  PubMed  Google Scholar 

  38. Otukesh H, Fereshtehnejad SM, Hoseini R et al (2009) Urine macrophage migration inhibitory factor (MIF) in children with urinary tract infection: a possible predictor of acute pyelonephritis. Pediatric Nephrology 24:105–111

    Article  PubMed  Google Scholar 

  39. Makita H, Nishimura M, Miyamoto K et al (1998) Effect of anti-macrophage migration inhibitory factor antibody on lipopolysaccharide-induced pulmonary neutrophil accumulation. Am J Respir Crit Care Med 158:573–579

    Article  PubMed  CAS  Google Scholar 

  40. Pollak N, Sterns T, Echtenacher B, Mannel DN (2005) Improved resistance to bacterial superinfection in mice by treatment with macrophage migration inhibitory factor. Infect Immun 73:64884–64892

    Article  Google Scholar 

  41. Yende S, Angus DC, Kong L et al (2009) The influence of macrophage migration inhibitory factor gene polymorphisms on outcome from community-acquired pneumonia. FASEB J 23:2403–2411

    Article  PubMed  CAS  Google Scholar 

  42. Lehmann LE, Novender U, Schroeder S et al (2001) Plasma levels of macrophage migration inhibitory factor are elevated in patients with severe sepsis. Intensive Care Med 27:1412–1415

    Article  PubMed  CAS  Google Scholar 

  43. de Mendonca-Filho HT, Gomes RV, de Almeida Campos LA et al (2004) Circulating levels of macrophage migration inhibitory factor are associated with mild pulmonary dysfunction after cardiopulmonary bypass. Shock 22:533–537

    Article  PubMed  Google Scholar 

  44. Kofoed K, Andersen O, Kronborg G et al (2007) Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study. Crit Care 11:R38

    Article  PubMed  Google Scholar 

  45. Grieb G, Simons D, Piatkowski A, Bernhagen J, Steffens GC, Pallua N (2009) Macrophage migration inhibitory factor-A potential diagnostic tool in severe burn injuries? Burns 36:335–342

    Article  PubMed  Google Scholar 

  46. Chagnon F, Metz CN, Bucala R, Lesur O (2005) Endotoxin-induced myocardial dysfunction: Effects of macrophage migration inhibitory factor neutralization. Circ Res 96:1095–1102

    Article  PubMed  CAS  Google Scholar 

  47. Gao XM, Liu Y, White D et al (2011) Deletion of macrophage migration inhibitory factor protects the heart from severe ischemia-reperfusion injury: a predominant role of anti-inflammation. J Mol Cell Cardiol 50:991–999

    Article  PubMed  CAS  Google Scholar 

  48. Yu CM, Lai KW, Chen YX, Huang XR, Lan HY (2003) Expression of macrophage migration inhibitory factor in acute ischemic myocardial injury. J Histochem Cytochem 51:625–631

    Article  PubMed  CAS  Google Scholar 

  49. Stoppe C, Fries M, Rossaint R et al (2012) Blood levels of macrophage migration inhibitory factor after successful resuscitation from cardiac arrest. PLoS One 7:e33512

    Article  PubMed  CAS  Google Scholar 

  50. Amin MA, Volpert OV, Woods JM, Kumar P, Harlow LA, Koch AE (2003) Migration inhibitory factor mediates angiogenesis via mitogen-activated protein kinase and phosphatidylinositol kinase. Circ Res 93:321–329

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements:

Without naming them individually, we are very thankful to numerous friends and colleagues with whom we have shared our research on MIF and who have helped us with valuable comments over many years. Furthermore, we are indebted to the technical assistance of M. Coeuru for designing the figures.

Author information

Authors and Affiliations

  1. Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany

    C. Stoppe & J. Bernhagen

  2. University Hospitals Gasthuisberg, Department of Anesthesiology, KU Leuven, Herestraat 49, 3000, Leuven, Belgium

    S. Rex

Authors
  1. C. Stoppe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Bernhagen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Rex
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Stoppe .

Editor information

Editors and Affiliations

  1. Erasme Hospital, Université libre de Bruxelles, Brussels, Belgium

    Jean-Louis Vincent Prof.

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Stoppe, C., Bernhagen, J., Rex, S. (2013). Macrophage Migration Inhibitory Factor in Critical Illness: Dr. Jekyll and Mr. Hyde?. In: Vincent, JL. (eds) Annual Update in Intensive Care and Emergency Medicine 2013. Annual Update in Intensive Care and Emergency Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-35109-9_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-35109-9_13

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-35108-2

  • Online ISBN: 978-3-642-35109-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation