Differential intragraft cytokine messenger RNA profiles during rejection and repair of clinical heart transplants. A longitudinal study.
After clinical heart transplantation, ischemia, acute rejection, and repair mechanisms can trigger the up-regulation of cytokines. To investigate the cytokine profile early after transplantation, we monitored messenger RNA (mRNA) expression levels of tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-beta (TGF-beta), platelet-derived growth factor-A (PDGF-A), and basic fibroblast growth factor (bFGF) by reverse transcriptase-polymerase chain reaction (RT-PCR) in serial endomyocardial biopsies ( n=123) from 16 cardiac allograft recipients during the first 3 post-operative months. In the first month, mRNA expression levels of MCP-1, TNF-alpha, TGF-beta, and bFGF were significantly higher than in the period thereafter (acute rejection episodes excluded). Acute rejection (International Society for Heart and Lung Transplantation (ISHLT) rejection grade >2) was strongly associated with the level of TNF-alpha mRNA. After acute rejection episodes, rising mRNA expression levels of PDGF-A and bFGF were found. The association between TNF-alpha mRNA and acute rejection reflects the importance of this cytokine in allogeneic responses. Elevated growth factor expression levels indicate repair responses after tissue damage due to either the transplantation procedure (surgery, ischemia, reperfusion) or acute allograft rejection.
de Groot-Kruseman
Hester A
HA
Department of Internal Medicine, Erasmus MC, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
Mol
Wendy M
WM
Niesters
Hubert G M
HG
Maat
Alex P W
AP
van Gelder
Teun
T
Balk
Aggie H M M
AH
Weimar
Willem
W
Baan
Carla C
CC
D000208:Acute Disease; D001706:Biopsy; D018932:Chemokine CCL2 / Q000235:genetics; D003080:Cold Temperature; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D015870:Gene Expression / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D016027:Heart Transplantation; D006801:Humans; D008137:Longitudinal Studies; D017202:Myocardial Ischemia / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D018932:Chemokine CCL2; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C075278:platelet-derived growth factor A; D016222:Fibroblast Growth Factor 2