title: Removal of soluble biologic response modifiers (complement and chemokines) by a bedside white cell-reduction filter.
abstract: BACKGROUND
  Biologic response modifiers infused with stored platelet concentrates (PCs) are believed to contribute to symptoms seen during transfusion reactions. Although prestorage white cell reduction is known to decrease the production of some biologic response modifiers during storage, the possibility that poststorage (bedside) white cell reduction could reduce the amount of biologic response modifiers already present in stored PCs during bedside filtration has not been well studied.
  
  
  METHODS
  Individual PCs were pooled on storage Days 2 and 5 and passed through a third-generation white cell-reduction filter. The results from a series of in vitro PC assays were studied, before and immediately after filtration, as were levels of C3a and interleukin 8 (n = 5). Levels of other biologic response modifiers-C5a, interleukin 1 beta, interleukin 6, tumor necrosis factor alpha, and RANTES-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 log10 reduction in white cells was reliably seen after filtration in Day 2 and 5 pooled PCs. Postfiltration platelet loss was 14.8 percent for Day 2 pooled PCs and 9.6 percent for Day 5 pooled PCs. For pools of both Day 2 and Day 5 platelets, postfiltration levels of CD62 (P-selectin, CD62P) were unchanged from prefiltration levels, as were results for morphology scores. Levels of C3a decreased after filtration in 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 filtration vs. 124 ng/mL after filtration). Levels of interleukin 8 were similarly 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 filtration). Levels of interleukin 8 in other components evaluated after filtration declined similarly. However, levels of the proinflammatory cytokines interleukin 1 beta and interleukin 6 did not decline after filtration. Serial filtration studies showed that, although levels of interleukin 8 and RANTES were initially lowered by filtration, they returned to prefiltration values with increases in the volume of filtration.
  
  
  CONCLUSIONS
  The third-generation bedside filter used in this study reliably reduced the level of white cell contamination to 4 log10 white cells per PC. It also lowered the levels of interleukin 8, RANTES, and C3a. The filter did not, however, remove (scavenge) the proinflammatory cytokines interleukin 1 beta and 6. The mechanism of chemokine and C3a removal by the filter is unknown, but it may be related to ionic interactions between these biologic response modifiers and the filter medium.
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, Yale-New Haven Hospital, CT, USA.
authors.forename: E L
authors.initials: EL
authors.lastname: Snyder
authors.forename: S
authors.initials: S
authors.lastname: Mechanic
authors.forename: L
authors.initials: L
authors.lastname: Baril
authors.forename: R
authors.initials: R
authors.lastname: Davenport
mesh_terms: D001803:Blood Transfusion; D002469:Cell Separation; D018946:Chemokine CCL5 / Q000302:isolation & purification; D015926:Complement C3a / Q000302:isolation & purification; D005374:Filtration; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007155:Immunologic Factors / Q000302:isolation & purification*; D016209:Interleukin-8 / Q000302:isolation & purification; D007962:Leukocytes
chemical_list: D018946:Chemokine CCL5; D007155:Immunologic Factors; D016209:Interleukin-8; D015926:Complement C3a