Elimination of cytokine production in stored platelet concentrate aliquotsby photochemical treatment with psoralen plus ultraviolet A light

BACKGROUND: Cytokines generated in platelet concentrates (PCs) during stora ge have been implicated as possible mediators of febrile nonhemolytic trans fusion reactions. Two potential methods of white cell inactivation were com pared for their ability to reduce cytokine synthesis in pooled random-donor PC aliquots: treatment with gamma-radiation and photochemical treatment (P CT) using psoralens and ultraviolet A light. STUDY DESIGN AND METHODS: ABO-matched PC aliquots were pooled and divided i nto separate aliquots. Aliquots (20 mt) were taken from each pool to serve as an untreated control and to undergo gamma-radiation. Aliquots were treat ed 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 a nalyzed for levels of interleukin 8 by use of an enzyme-linked immunosorben t assay. Levels of DNA adduct formation were determined by using H-3-labele d 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 reducti on in cytokine synthesis (p<0.05). Day 5 to 7 levels of interleukin 8 did n ot differ significantly from Day 0 levels. Inhibition of interleukin 8 prod uction by PCT increased with increasing levels of DNA modification (S-59 > AMT > 8-MOP). CONCLUSION: PCT that utilizes S-59 has been developed to inactivate potenti al 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-assoc iated febrile nonhemolytic transfusion reactions.