Transfusion-induced leukocyte IL-8 gene expression is avoided by the use of human polymerized hemoglobin

Forest R. Sheppard, Ernest E. Moore, Jeffrey L. Johnson, Aaron M. Cheng, Nathan McLaughlin, Christopher C. Silliman, Avery B. Nathens, Edwin A. Deitch, Carl J. Hauser, Peter Rhee

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10 Scopus citations

Abstract

Background: 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. Methods: 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°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/μg total RNA ± SEM. Stats: ANOVA with Bonferroni/Dunn post hoc analysis. Results: Simulated transfusion of pRBCs increased TL IL-8 mRNA (RB = 0.28 ± 0.10 amol/μg total RNA, RB + pRBC = 2.24 ± 0.25 amol/μg total RNA, p < 0.01), whereas PolyHb did not (B + PolyHb = 0.82 ± 0.30 amol/μg 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/μg total RNA, RB + pRBC = 7.60 ± 1.79 amol/μg total RNA, p < 0.01), whereas PolyHb did not (RB + PolyHb = 4.53 ± 1.64 amol/μg total RNA). Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)720-725
Number of pages6
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume57
Issue number4
DOIs
StatePublished - Oct 1 2004

Keywords

  • Blood Substitute
  • Hemoglobin
  • Interleukin-8
  • Neutrophil
  • Transfusion

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

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    Sheppard, F. R., Moore, E. E., Johnson, J. L., Cheng, A. M., McLaughlin, N., Silliman, C. C., Nathens, A. B., Deitch, E. A., Hauser, C. J., & Rhee, P. (2004). Transfusion-induced leukocyte IL-8 gene expression is avoided by the use of human polymerized hemoglobin. Journal of Trauma - Injury, Infection and Critical Care, 57(4), 720-725. https://doi.org/10.1097/01.TA.0000140479.65350.28