Myocardial IL-6 regulation by neurohormones--an in vitro superfusion study.
BACKGROUND
Interleukin-6 (IL-6) is expressed in the myocardium and has been implicated in cell proliferation, negative inotropic effects and myocardial hypertrophy. To determine whether myocardial IL-6 is modified by neurohumoral and immunoregulatory stimuli, we studied the effects of lipopolysaccharide (LPS), corticosterone (CS), isoproterenol and angiotensin II on myocardial IL-6 secretion in superfused myocardium.


METHODS
Slices of rat left ventricular myocardium were superfused in 80 microl chambers for up to 5h. LPS (1, 50, and 100 microg/ml), CS (10(-7), 10(-6), and 10(-5)M, DSMO as vehicle), isoproterenol (10(-6), 10(-7), and 10(-8)M) and angiotensin II (10(-5), 10(-7), and 10(-9)M) were added to the culture medium at hour 2. IL-6 was measured in the perfusate by ELISA.


RESULTS
Physiological corticosterone concentrations (10(-7)M) resulted in an increase in IL-6 concentration (142%) while high doses of steroid decreased IL-6 significantly (CS 10(-6)M: 88+/-14%,p<.05; CS 10(-5): 91+/-9%,p<.05) after 5h. Left ventricular IL-6 secretion was significantly stimulated by LPS 50 microg/ml (3262+/-1684% vs. CTRL: 116+/-34%, p<.01). Isoproterenol treatment increased in IL-6 secretion compared to controls with and without CS, while angiotensin II reduced IL-6 concentration only in combination with CS.


CONCLUSIONS
Myocardial IL-6 secretion is modulated by physiological concentrations of corticosterone or angiotensin II and can be induced by LPS or isoproterenol, indicating a tight regulation of this cytokine. Suppression of cytokine expression within the heart might be a potential therapeutic goal in the treatment of various cardiovascular diseases.
Jeron
Andreas
A
Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany. andreas.jeron@klinik.uni-regensburg.de
Kaiser
Tanja
T
Straub
Rainer H
RH
Weil
Joachim
J
Riegger
Günter A J
GA
Muders
Frank
F
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D003345:Corticosterone / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015850:Interleukin-6 / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009924:Organ Culture Techniques; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D002316:Cardiotonic Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000804:Angiotensin II; D007545:Isoproterenol; D003345:Corticosterone