REMOVAL OF SOLUBLE BIOLOGIC RESPONSE MODIFIERS (COMPLEMENT AND CHEMOKINES) BY A BEDSIDE WHITE CELL-REDUCTION FILTER

Background: Biologic response modifiers infused with stored platelet c oncentrates (PCs) are believed to contribute to symptoms seen during t ransfusion reactions. Although prestorage white cell reduction is know n to decrease the production of some biologic response modifiers durin g storage, the possibility that poststorage (bedside) white cell reduc tion could reduce the amount of biologic response modifiers already pr esent in stored PCs during bedside filtration has not been well studie d. Study Design and Methods: Individual PCs were pooled on storage Day s 2 and 5 and passed through a third-generation white cell-reduction f ilter. The results from a series of in vitro PC assays were studied, b efore and immediately after filtration, as were levels of C3a and inte rleukin 8 (n = 5). Levels of other biologic response modifiers-C5a, in terleukin 1 beta, interleukin 6, tumor necrosis factor alpha, and RANT ES-were also studied. Removal of interleukin 8 and RANTES was studied further by using serial filtration of units of PC. Results: For the in vitro platelet assays studied, pH was unchanged after filtration from prefiltration values in units of PCs pooled on storage Day 2 or 5. A 4 log(10) reduction in white cells was reliably seen after filtration in Day 2 and 5 pooled PCs. Postfiltration platelet loss was 14.8 perce nt for Day 2 pooled PCs and 9.6 percent for Day 5 pooled PCs. For pool s of both Day 2 and Day 5 platelets, postfiltration levels of CD62 (P- selectin, CD62P) were unchanged from prefiltration levels, as were res ults for morphology scores. Levels of C3a decreased after filtration i n both the Day 2 pooled PCs (448 ng/mL before filtration vs. 20 ng/mL after filtration) and the Day 5 pooled PCs (1976 ng/mL before filtrati on vs. 124 ng/mL after filtration). Levels of interleukin 8 were simil arly reduced after filtration in the Day 2 pooled platelets (188 pg/mL before filtration vs. 27 pg/mL after filtration) and the Day 5 pooled platelets (2234 pg/mL before filtration vs. 799 pg/mL after filtratio n). Levels of interleukin 8 in other components evaluated after filtra tion declined similarly. However, levels of the proinflammatory cytoki nes interleukin 1 beta and interleukin 6 did not decline after filtrat ion. Serial filtration studies showed that, although levels of interle ukin 8 and RANTES were initially lowered by filtration, they returned to prefiltration values with increases in the volume of filtration. Co nclusion: The third-generation bedside filter used in this study relia bly reduced the level of white cell contamination to 4 log(10) white c ells per PC. It also lowered the levels of interleukin 8, RANTES, and C3a. The filter did not, however, remove (scavenge) the proinflammator y cytokines interleukin 1 beta and 6. The mechanism of chemokine and C 3a removal by the filter is unknown, but it may be related to ionic in teractions between these biologic response modifiers and the filter me dium.