Immune cytokine inhibition of beta-adrenergic agonist stimulated cyclic AMP generation in cardiac myocytes.
We hypothesize that reversible depression of cardiac function in cardiac allograft rejection and lymphocytic myocarditis reflects down modulation of the beta-adrenergic receptor system by a soluble product of activated immune cells. Thus, exposure of cultured cardiac myocytes to mixed lymphocyte culture or activated splenocyte supernatants produces 70% inhibition of isoproterenol-stimulated cAMP concentrations (Ki = 5% supernatant) in the absence of gross cellular injury or control media effects. This cAMP suppressive factor is not dialyzable and is ammonium sulfate precipitable. Beta-adrenergic receptor density, binding constant and affinity states are unaffected. These results demonstrate the existence of a cytokine inhibitor of cAMP accumulation that may mediate, in part, depression of cardiac contractility observed when immune cells invade the myocardium.
Gulick
T
T
Department of Medicine, Jewish Hospital of St. Louis, Washington University Medical Center, Missouri 63110.
Chung
M K
MK
Pieper
S J
SJ
Schreiner
G F
GF
Lange
L G
LG
D000818:Animals; D000831:Animals, Newborn; D001688:Biological Products / Q000494:pharmacology*; D002478:Cells, Cultured; D003470:Culture Media; D000242:Cyclic AMP / Q000096:biosynthesis*; D016207:Cytokines; D007545:Isoproterenol / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D013154:Spleen / Q000166:cytology
D001688:Biological Products; D003470:Culture Media; D016207:Cytokines; D011943:Receptors, Adrenergic, beta; C047975:cyanopindolol; D010869:Pindolol; D000242:Cyclic AMP; D007545:Isoproterenol