CLINCAL STUDY: HEART TRANSPLANTATION
The interleukin-6/interleukin-6-receptorsystem is activated in donor hearts
Gabriele Plenz, PhD, MSc*  ,*,
Heike Eschert, PhD, MSc*,
Michael Erren, MD ,
Thomas Wichter, MD,
Michael Böhm, MD||,
Markus Flesch, MD¶,
Hans H. Scheld, MD* and
Mario C. Deng, MD, FACC, FESC*#
* Department of Cardiothoracic Surgery, Muenster University, Muenster, Germany
Department of Cardiology and Angiology, Muenster University, Muenster, Germany
Institute for Arteriosclerosis Research, Muenster University, Muenster, Germany
Institute of Laboratory Medicine, Muenster University, Muenster, Germany
|| University Homburg/Saar, Homburg/Saar, Germany
¶ Baylor College of Medicine, Houston, Texas, USA
# Columbia University, New York, New York, USA
Manuscript received March 26, 2001;
revised manuscript received January 24, 2002,
accepted February 6, 2002.
* Reprint requests and correspondence: Dr. Gabriele Plenz, Department of Cardiothoracic Surgery, Muenster University, Albert-Schweitzer-Str. 33, D-48149 Muenster, Germany.
plenz{at}uni-muenster.de
OBJECTIVES: To assess the potential of the donor heart to respond to interleukin-6 (IL6), the present study investigated the expression of IL6 receptor components in the myocardium of donor hearts before transplantation.
BACKGROUND: Donor heart dysfunction early after transplantation has been associated with the cytokine storm after donor brain death. Proinflammatory cytokines are thought to play a central role in this process. Interleukin-6 is of specific interest because it has been associated with cardiac allograft dysfunction and is related to an impaired prognosis. Its action requires expression of the specific IL6 receptor (IL6R), and the common signal transducer of the IL6 family glycoprotein 130 (gp130) in the donor heart.
METHODS: The activation of IL6, IL6R and gp130 messenger ribonucleic acid (mRNA) and protein was studied via reverse transcription-polymerase chain reaction (RT-PCR) and immunohistology in donor hearts (n = 6) and compared with patients undergoing evaluation of ventricular arrhythmias (control, n = 9) or with advanced heart failure (n = 20).
RESULTS: Messenger RNA of IL6, IL6R and gp130 was strongly expressed in all chambers of donor hearts, whereas right ventricles of control patients did not show any expression (donor vs. control: p < 0.005). Right ventricles of failing hearts showed IL6, IL6R and gp130 mRNA levels comparable with those found in donor hearts. Immunohistochemistry paralleled the RT-PCR data on the protein level. While IL6 was mainly expressed by myocytes, both receptor components were preferentially found mainly on interstitial cells.
CONCLUSIONS: The expression of the IL6 receptor components in the donor heart before transplantation establishes the condition sine qua non for the response of the donor heart to circulating IL6. This mechanism may explain the close association of elevated IL6 serum levels to acute cardiac allograft dysfunction in the early perioperative period.
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Abbreviations and Acronyms
| | bp | | base pair | | gp130 | | glycoprotein 130 | | G3PDH | | glyceraldehyde-3-phosphate-dehydrogenase | | IL6 | | interleukin-6 | | IL6R | | interleukin-6-receptor | | mRNA | | messenger ribonucleic acid | | PCR | | polymerase chain reaction | | RT-PCR | | reverse transcription-polymerase chain reaction | | RV | | right ventricular |
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