Prognostic value of platelet-derived growth factor in patients with severe sepsis.
OBJECTIVE
Platelet-derived growth factor-BB (PDGF-BB) has been shown to promote the structural integrity of the vessel wall and to increase wound healing capacity. Aim of the present study was to determine the role of PDGF-BB in the context of outcome of septic patients. Furthermore, the effect of treatment with recombinant human activated protein C (rhAPC) on plasma levels of PDGF-BB in severe sepsis was evaluated as well as the in vitro effect of rhAPC on PDGF-BB-release from human endothelial cells (HUVEC). RESEARCH DESIGN, METHODS AND PROCEDURES: PDGF-BB levels were measured in 46 patients on day 3 of severe sepsis. Twenty-one of these patients received treatment with rhAPC. The in vitro effect of rhAPC on PDGF-BB-messenger RNA synthesis and release of PDGF-BB into supernatants was measured by reverse transcriptase-polymerase chain reaction and ELISA-methods.


RESULTS
Survivors of severe sepsis presented with higher PDGF-BB levels than non-survivors (p < 0.05). Septic patients with PDGF-BB levels below 200 pg/ml were 7.3 times more likely (RR = 7.3, 95% CI: 1.4-44.5; p < 0.05) to die from sepsis than patients with higher PDGF-BB values. RhAPC (1-10 microg/ml) stimulated endothelial PDGF-BB-messenger RNA transcription and PDGF-BB-release in vitro. Plasma levels of PDGF-BB in patients receiving rhAPC were significantly (p < 0.01) higher (median 277.7; 25-75th percentiles: 150.5-414.4 pg/ml) than in patients not treated with rhAPC (median: 125.6; 25-75th percentiles: 55.3-344.7 pg/ml).


CONCLUSIONS
The ability of rhAPC to upregulate endothelial PDGF-BB production may represent a new molecular mechanism by which rhAPC controls vessel wall homeostasis and increases tissue healing capacity in severe sepsis. PDGF-BB may serve as useful laboratory marker to predict survival in patients presenting with severe sepsis.
Brueckmann
Martina
M
First Department of Medicine, Faculty of Medicine Mannheim, University of Heidelberg. Mannheim, Germany. martina.brueckmann@med.ma.uni-heidelberg.de
Hoffmann
Ursula
U
Engelhardt
Cathleen
C
Lang
Siegfried
S
Fukudome
Kenji
K
Haase
Karl K
KK
Liebe
Volker
V
Kaden
Jens J
JJ
Putensen
Christian
C
Borggrefe
Martin
M
Huhle
Guenter
G
D000328:Adult; D000368:Aged; D015703:Antigens, CD; D001483:Base Sequence; D000077214:Becaplermin; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D000074283:Endothelial Protein C Receptor; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D011486:Protein C / Q000627:therapeutic use; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000627:therapeutic use; D018805:Sepsis / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D010975:Platelet Aggregation Inhibitors
D015703:Antigens, CD; D017931:DNA Primers; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D010982:Platelet-Derived Growth Factor; D011486:Protein C; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D000077214:Becaplermin; C421124:drotrecogin alfa activated; D010975:Platelet Aggregation Inhibitors