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Transfusion-Induced Leukocyte IL-8 Gene Expression is Avoided by the Use of Human Polymerized Hemoglobin

2004; Lippincott Williams & Wilkins; Volume: 57; Issue: 4 Linguagem: Inglês

10.1097/01.ta.0000140479.65350.28

1529-8809

Forest R. Sheppard, Ernest E. Moore, Jeffrey L. Johnson, Aaron M. Cheng, Nathan McLaughlin, Christopher C. Silliman,

Hemoglobin structure and function

Red blood cell (pRBC) transfusion is an independent risk factor for multiple organ failure (MOF); a maladaptive immuno-inflammatory response is implicated. Interleukin-8 (IL-8) is one putative mediator of this response. We previously observed that injured patients resuscitated with pRBCs have increased plasma IL-8 compared with those given human polymerized hemoglobin (PolyHb). To further elucidate the mechanisms responsible for this difference in IL-8, we devised an ex-vivo transfusion model. We hypothesize that pRBC transfusion induces increased IL-8 gene expression that is avoided by the use of PolyHb.Human volunteer blood was incubated alone (RB) or with a major transfusion (50% exchange) of either post-storage leukoreduced O-pRBCs (RB + pRBC) or PolyHb (RB + PolyHb) for 30 minutes at 37 degrees C. Total leukocyte (TL) or polymorphonuclear leukocyte (PMN) total RNA was isolated and IL-8 mRNA quantified. Results are reported as amol IL-8 mRNA/microg total RNA +/- SEM. Stats: ANOVA with Bonferroni/Dunn post hoc analysis.Simulated transfusion of pRBCs increased TL IL-8 mRNA (RB=0.28 +/- 0.10 amol/microg total RNA, RB + pRBC=2.24 +/- 0.25 amol/microg total RNA, p <0.01), whereas PolyHb did not (B + PolyHb=0.82 +/- 0.30 amol/microg total RNA). PolyHb IL-8 mRNA was less than pRBC transfused (p <0.01). In PMNs, simulated transfusion of pRBCs increase IL-8 mRNA (RB=3.17 +/- 1.05 amol/microg total RNA, RB + pRBC=7.60 +/- 1.79 amol/microg total RNA, p <0.01), whereas PolyHb did not (RB + PolyHb=4.53 +/- 1.64 amol/microg total RNA).Stored pRBCs induces increased TL and PMN IL-8 gene expression, whereas human polymerized hemoglobin, in lieu or pRBCs, avoids this increase. These experimental results corroborate our previous clinical studies and further encourage the study of PolyHb as a resuscitation strategy to decrease postinjury MOF.