Effects of IL-2 on the myocardium. Participation of the sympathetic system.
IL-2 is known to have various effects outside the frame of the immune system and it could have a role as an autocrine modulatory agent in certain cardiac dysfunctions associated to inflammatory cell infiltration of the heart. In this study, by means of binding assays on cardiac membranes or by evaluating contractility and cAMP levels of isolated rat atria in the presence of IL-2, we demonstrate that IL-2 may indirectly stimulate beta-adrenergic-mediated function by triggering the presynaptic release of norepinephrine (NE) on isolated rat atria. Thus it reacts with cardiac tissue inducing a positive inotropic response that can be blocked by the beta-adrenergic antagonist propranolol but not by phentolamine. Binding of the beta-adrenergic antagonist CGP 12177 is not affected by IL-2. Furthermore, chemical sympathectomy with 6-hydroxydopamine (6-OHDA) prevents the inotropic effect of IL-2, while cocaine treatment sensitizes atria to IL-2, indicating that NE secretion is required, and that the beta-adrenergic effect of IL-2 is presynaptic. In addition, IL-2 mimics beta-adrenergic stimulation increasing cAMP synthesis. Colchicine inhibited cAMP stimulation as well as positive inotropism, and both effects of IL-2 were additive with isoproterenol. However, cAMP synthesis could only be partially blocked by propranolol, suggesting that IL-2 stimulated cAMP synthesis both by a direct, beta-adrenergic independent mechanism and by a beta-adrenergic dependent pathway. We conclude that IL-2 induces a positive inotropic response in isolated rat atria through two different pathways: an indirect activation of myocardial beta-adrenergic receptors by releasing catecholamines and a direct action by increasing the production of the second messenger cAMP.
Sterin-Borda
L
L
CEFYBO-CONICET, Department of Pharmacology, School of Dentistry and Medicine, University of Buenos Aires, Argentina.
Perez Leiros
C
C
Borda
E S
ES
de Bracco
M M
MM
D000818:Animals; D016275:Atrial Function; D000242:Cyclic AMP / Q000096:biosynthesis; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology
D007376:Interleukin-2; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP