Evidence for de novo synthesis of cytokines and chemokines in platelet concentrates.
OBJECTIVE
Inflammatory cytokines in platelet concentrates (PC) may cause side-effects such as febrile non-haemolytic transfusion reactions. The maximum white blood cell (WBC) content tolerable to avoid the accumulation of cytokines, and whether these cytokines originate from degranulating leucocytes or de novo synthesis during storage, had not been investigated prior to this study.


METHODS
We investigated the secretion of interleukin (IL)-1beta, IL-2, IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) and quantified the appropriate expression of corresponding mRNA in PC with regard to different levels of WBC contamination and storage times. In addition we tested the viability of WBCs during PC storage (by staining with 7-aminoactinomycin D) and their ability to perform de novo cytokine synthesis (by using superantigen stimulation).


RESULTS
We detected a statistically significant increase of IL-1beta, IL-6, IL-8 and TNF-alpha in PC with > or = 108 WBCs. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) showed increasing mRNA expression of the respective cytokines depending on the number of WBC present. On day 5 of storage, WBC viability was > 80% and the leucocytes were still able to produce cytokines de novo.


CONCLUSIONS
These data show clear evidence for de novo synthesis of cytokines in PC. The cytokine pattern supports the hypothesis that activated monocytes are responsible for this cytokine synthesis. PC with a WBC contamination of > or = 108 contain inflammatory mediators in clinically relevant concentrations.
Hartwig
D
D
Institute of Immunology and Transfusion Medicine, University of Lübeck School of Medicine, Germany. hartwig@immu.mu-luebeck.de
Härtel
C
C
Hennig
H
H
Müller-Steinhardt
M
M
Schlenke
P
P
Klüter
H
H
D001792:Blood Platelets / Q000276:immunology*; D018929:Cell Culture Techniques; D018925:Chemokines / Q000009:adverse effects / Q000096:biosynthesis* / Q000276:immunology; D016207:Cytokines / Q000009:adverse effects / Q000096:biosynthesis* / Q000276:immunology; D017931:DNA Primers; D020869:Gene Expression Profiling; D006801:Humans; D017713:Platelet Transfusion / Q000009:adverse effects*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013048:Specimen Handling
D018925:Chemokines; D016207:Cytokines; D017931:DNA Primers; D012333:RNA, Messenger