Elimination of cytokine production in stored platelet concentrate aliquots by photochemical treatment with psoralen plus ultraviolet A light.
BACKGROUND
Cytokines generated in platelet concentrates (PCs) during storage have been implicated as possible mediators of febrile nonhemolytic transfusion reactions. Two potential methods of white cell inactivation were compared for their ability to reduce cytokine synthesis in pooled random-donor PC aliquots: treatment with gamma-radiation and photochemical treatment (PCT) using psoralens and ultraviolet A light.


METHODS
ABO-matched PC aliquots were pooled and divided into separate aliquots. Aliquots (20 mL) were taken from each pool to serve as an untreated control and to undergo gamma-radiation. Aliquots were treated by using either gamma-radiation (2500 or 5000 cGy) or virucidal PCT. PCT with the psoralens 8-methoxypsoralen (8-MOP), aminomethyltrimethyl psoralen (AMT), and S-59 was investigated. PC aliquots were stored for 7 days and analyzed for levels of interleukin 8 by use of an enzyme-linked immunosorbent assay. Levels of DNA adduct formation were determined by using 3H-labeled psoralens.


RESULTS
Levels of interleukin 8 in the untreated random-donor PC aliquots increased with increasing white cell counts, but they were not affected by pooling. The untreated control aliquots and the aliquots treated with gamma-radiation had significant increases in levels of interleukin 8 after 5 to 7 days of storage (p<0.05). PCT with S-59 resulted in a significant reduction in cytokine synthesis (p<0.05). Day 5 to 7 levels of interleukin 8 did not differ significantly from Day 0 levels. Inhibition of interleukin 8 production by PCT increased with increasing levels of DNA modification (S-59 > AMT > 8-MOP).


CONCLUSIONS
PCT that utilizes S-59 has been developed to inactivate potential viral and bacterial pathogens in PC aliquots while maintaining in vitro platelet function. These data demonstrate that PCT of aliquots of pooled PC aliquots before storage also prevents white cell cytokine synthesis during storage. PCT may therefore offer the potential for reducing cytokine-associated febrile nonhemolytic transfusion reactions.
Hei
D J
DJ
Cerus Corp, Concord, California 94520, USA.
Grass
J
J
Lin
L
L
Corash
L
L
Cimino
G
G
D001793:Blood Preservation; D016207:Cytokines / Q000097:blood; D018736:DNA Adducts / Q000097:blood; D003864:Depression, Chemical; D004797:Enzyme-Linked Immunosorbent Assay; D005363:Ficusin / Q000494:pharmacology; D011564:Furocoumarins / Q000097:blood; D005720:Gamma Rays; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D007962:Leukocytes / Q000737:chemistry / Q000187:drug effects* / Q000528:radiation effects; D008730:Methoxsalen / Q000494:pharmacology*; D017713:Platelet Transfusion / Q000009:adverse effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013997:Time Factors; D014307:Trioxsalen / Q000031:analogs & derivatives* / Q000494:pharmacology; D014466:Ultraviolet Rays
D016207:Cytokines; D018736:DNA Adducts; D011564:Furocoumarins; D016209:Interleukin-8; D011838:Radiation-Sensitizing Agents; C056465:psoralen-DNA adduct; C018822:aminomethyltrioxsalen; C118577:amotosalen; D005363:Ficusin; D008730:Methoxsalen; D014307:Trioxsalen