Mechanisms and new approaches for the allogeneic blood transfusion-induced immunomodulatory effects

Kao, Kuo-Jang

doi:10.1016/s0887-7963(00)80112-1

Cited by 36 publications

(33 citation statements)

References 104 publications

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“…Direct (15). In addition, in vitro allogeneic PRBC transfusion appears to have the potential to promote polymorphonuclear cell-mediated cytotoxicity and to suppress neutrophil locomotion (16) and apoptosis (17).…”

Section: Discussionmentioning

confidence: 99%

Plasma cytokines and markers of endothelial activation increase after packed red blood cell transfusion in the preterm infant

et al. 2012

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Background: Transfusion of packed red blood cells (PRBcs) saves lives in the neonatal critical care setting and is one of the most common interventions in the preterm infant. The number and volume of PRBc transfusions are associated with several major neonatal morbidities, although a direct causal link between transfusion and major neonatal morbidity is still to be proven. Transfusion-related immunomodulation (TRIM) may underlie these adverse outcomes, yet it has received little attention in the high-risk preterm infant. Methods: One transfusion event was studied in infants ≤28 wk gestation between 2 and 6 wk postnatal age (n = 28). Plasma inflammatory cytokines and markers of endothelial activation were measured in the infants before and 2-4 h after transfusion, as well as in the donor pack. results: Median (range) age at transfusion was 18 (14-39) days with the pretransfusion hemoglobin level at 9.8 (7.4-10.2) g/dl. Interleukin (IL)-1β (P = 0.01), IL-8 (P = <0.001), tumor necrosis factor-α (P = 0.008), and monocyte chemoattractant protein (P = 0.01) were increased after transfusion. a similar elevation in markers of endothelial activation was seen after transfusion with increased plasma macrophage inhibitory factor (P = 0.005) and soluble intracellular adhesion molecule-1 (P = <0.001). conclusion: Production of inflammatory cytokines and immunoactivation of the endothelium observed after the transfusion of PRBcs in the preterm infant may be a manifestation of TRIM. The implications of this emerging phenomenon within the preterm neonatal population warrant further investigation. t ransfusion of blood products is not benign. In adults, transfusion is an independent predictor of death and is associated with an increased incidence of multiorgan system failure, length of hospital stay, infection risk, and modulation of the immune system (1,2). Although the mechanisms underlying these associations are yet to be comprehensively characterized, a two-hit model of posttransfusion injury has been proposed (3). In the clinical setting of an underlying inflammatory state priming the recipient's immune system, transfusion of packed red blood cells (PRBCs) may trigger immune cell activation and related immunomodulation, resulting in frank inflammation (4). This transfusion-related immunomodulation (TRIM), encompassing not only adverse proinflammatory and immunosuppressive responses but also the whole spectrum of posttransfusion effects on organs and tissues, has been proposed to underlie much of the increased transfusionassociated morbidity and mortality seen in adults (4).In the neonatal population, there is an increasing awareness of the excess morbidity and mortality associated with PRBC transfusions (5,6). PRBC transfusions have been implicated in the development of problems not encountered in the adult population, including chronic lung disease (7), retinopathy of prematurity (8), and necrotizing enterocolitis (9,10), with the incidence and severity of these conditions correlating with the number and volume of PRBC tran...

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Section: Discussionmentioning

confidence: 99%

Plasma cytokines and markers of endothelial activation increase after packed red blood cell transfusion in the preterm infant

et al. 2012

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Section: Proposed Mechanisms Of Trimmentioning

confidence: 99%

“…8,69 The potential mechanisms proposed for the observed TRIM results from a number of different immunologic processes summarized in Table 2, which were the topic of a recent review. 8 Clonal deletion of cytotoxic T lymphocytes was suggested by the decreased appearance of the CTL precursors, which may have been caused by a unique population of donor leukocytes known as "veto" cells. 70,71 Although these studies appear attractive, further definition of these cells is vital; moreover, neither the clonal deletion of CTLs or decreased number of CTL precursors or anergy of these cells has been demonstrated in renal allograft recipients who had been transfused prior to transplantation.…”

Section: Proposed Mechanisms Of Trimmentioning

confidence: 99%

“…76 There is some limited data that suggests these antibodies are produced including in a human renal allograft recipient, but basic immunochemical studies to document their presence and antigen binding capabilities have not been completed rendering this hypothesis speculative. 8,77 Another attractive hypothesis is the reduction of natural killer (NK) cell activity. Transfusion of patients with sickle cell disease and patients undergoing colorectal surgery demonstrated a reduction in NK activity, which may be directly due to passenger leukocytes, for this reduction in NK activity was altered by leukoreduction.…”

Section: Proposed Mechanisms Of Trimmentioning

confidence: 99%

“…3 Despite these proven benefits, these findings prompted closer examination of the role of transfusion of cellular components in nonspecific alterations in the host immune system leading to transfusionrelated immunomodulation (TRIM) possibly predisposing patients to postoperative infection, activation of latent viral infections, and the growth and dissemination of malignant tumors. [4][5][6][7][8][9] In addition, in an effort to lessen the effects of TRIM, leukoreduction has been advocated, although the results of a number of randomized controlled trials designed to investigate the role of leukoreduction are mixed and no definitive conclusion may be reached. 10 Recently, the role of stored, versus fresh, cellular components has been explored such that the use of fresh cellular components may affect TRIM among different patient groups.…”

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Immunomodulatory Effects of Stored Packed Red Blood Cells in the Injured Patient

Silliman

2005

Transfus Alt Transfus Med

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Intravenous delivery of the plasma fraction of stored packed erythrocytes promotes pancreatic cancer growth in immunocompetent mice

Barnett

Beck

Holloway

et al. 2010

Cancer

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BACKGROUND: Perioperative blood transfusion in pancreatic cancer patients has been linked to decreased survival; however, a causal mechanism has not been determined. During the processing and storage of packed erythrocytes, biologically active molecules accumulated in the acellular plasma fraction; therefore, the authors hypothesized that the plasma fraction of stored packed erythrocytes promoted tumor progression. METHODS: Proliferation and migration of murine pancreatic cancer and control cells were determined in vitro in response to the plasma fraction from leukocyte and nonleukocyte-reduced fresh versus stored packed erythrocytes. Last, an immunocompetent murine model was used to assess the effect of the plasma fraction of stored and processed packed erythrocytes on pancreatic cancer progression. RESULTS: Incubation of pancreatic cancer cells with the plasma fraction of packed erythrocytes increased proliferation and migration. Intravenous delivery of the acellular plasma fraction to mice with pancreatic cancer significantly increased the tumor weight in both leukocyte-reduced and nonleukocyte-reduced packed-erythrocyte groups (P < .01), although tumor growth and morbidity were greatest in the nonleukocytereduced group. CONCLUSIONS: The plasma fraction of stored packed erythrocytes promoted murine pancreatic cancer proliferation and migration in vitro and when administered intravenously, significantly augmented pancreatic cancer growth in immunocompetent mice. Cancer 2010;116:3862-74.

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Mechanisms and new approaches for the allogeneic blood transfusion-induced immunomodulatory effects

Cited by 36 publications

References 104 publications

Plasma cytokines and markers of endothelial activation increase after packed red blood cell transfusion in the preterm infant

Plasma cytokines and markers of endothelial activation increase after packed red blood cell transfusion in the preterm infant

Immunomodulatory Effects of Stored Packed Red Blood Cells in the Injured Patient

Intravenous delivery of the plasma fraction of stored packed erythrocytes promotes pancreatic cancer growth in immunocompetent mice

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