Possible role of proinflammatory cytokines in heart allograft coronary artery disease.
Transplant coronary artery disease (Tx-CAD) is the main determinant of long-term prognosis after heart transplantation. Immunologic processes may play a central role in the development of Tx-CAD, but the pathogenesis has not been fully clarified. We examined plasma levels of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukins (IL)-1beta and IL-6, and the CC-chemokine macrophage chemoattractant protein-1 (MCP-1) in 62 cardiac allograft recipients undergoing yearly heart catherization with coronary angiography for evaluation of graft disease. In this cross-sectional study, we found significantly increased levels of IL-1beta, IL-6, TNF-alpha, and MCP-1 compared with healthy controls even several years (median 7 years) after transplantation in periods with no intercurrent illness. Although no significant differences were found in plasma levels of IL-1beta and TNF-alpha between patients with (n = 25) and without (n = 37) Tx-CAD, the Tx-CAD group had significantly increased levels of IL-6 and MCP-1 compared with both controls and transplant recipients without Tx-CAD. Increased IL-6 levels compared with controls were found only in patients with Tx-CAD. Finally, while there was no significant relation between Tx-CAD and altered lipid status, the combination of high plasma concentrations of IL-6 or MCP-1 and high low-density lipoprotein cholesterol was strongly associated with increased occurrence of Tx-CAD. These findings indicate that cardiac allograft recipients have a persistent immune activation long term after transplantation. This activation, as particularly reflected in increased MCP-1 and IL-6 levels, may be related to the development of Tx-CAD.
Gullestad
L
L
Department of Cardiology, and Research Institute for Internal Medicine, Rikshospitalet University Hospital, Oslo, Norway.
Simonsen
S
S
Ueland
T
T
Holm
T
T
Aass
H
H
Andreassen
A K
AK
Madsen
S
S
Geiran
O
O
Frøland
S S
SS
Aukrust
P
P
D000328:Adult; D000368:Aged; D018932:Chemokine CCL2 / Q000502:physiology; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000276:immunology*; D016207:Cytokines / Q000502:physiology*; D005260:Female; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000276:immunology*; D011379:Prognosis; D012307:Risk Factors; D014184:Transplantation, Homologous
D018932:Chemokine CCL2; D008078:Cholesterol, LDL; D016207:Cytokines; D015850:Interleukin-6