Impact of Injury Severity on the Inflammatory State and Severe Anemia

Miller, Elizabeth; Loftus, Tyler J.; Kannan, Kolenkode B.; Parvataneni, Hari K.; Hagen, Jennifer; Efron, Philip A.; Mohr, Alicia M.

doi:10.1016/j.jss.2019.10.046

Cited by 13 publications

(10 citation statements)

References 38 publications

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“…We investigated the correlation between AKI development and arterial levels of the early pro-infl ammatory cytokines interleukin-6 and procalcitonin. IL-6 levels early after injury correlated with the degree of anatomic injury as defi ned by ISS and predict subsequent complications including multiple organ dysfunction syndromes (including AKI) and mortality in previous reports (32,33). In our study, IL-6 was signifi cantly higher in the AKI-group at T2 and T3 but not at T1.…”

Section: Discussionsupporting

confidence: 63%

Physiologic risk factors for early acute kidney injury in severely injured patients

Sklienka¹,

Máca²,

Neiser³

et al. 2020

BLL

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Section: Discussionsupporting

confidence: 63%

Physiologic risk factors for early acute kidney injury in severely injured patients

Sklienka¹,

Máca²,

Neiser³

et al. 2020

BLL

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“…One study which cultured iliac crest bone marrow from trauma patients demonstrated BFU-E and CFU-E growth decline at supraphysiologic catecholamine levels, starting at 10 −7 M ( Fonseca et al, 2004 ). This is similar to levels of circulating norepinephrine measured in severely injured trauma patients with a mean of 44.1 ng/ml (2.6 × 10 −7 M) ( Apple et al, 2020a ). However, this decrease in erythroid progenitor cell growth was not observed in bone marrow depleted of stroma, suggesting that bone marrow stroma plays an essential role in the maturation of erythroid progenitor cells ( Fonseca et al, 2004 ).…”

Section: Mediators Of Persistent Anemia After Traumasupporting

confidence: 85%

Adrenergic Modulation of Erythropoiesis After Trauma

Munley

Kelly²,

Mohr³

2022

Front. Physiol.

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Severe traumatic injury results in a cascade of systemic changes which negatively affect normal erythropoiesis. Immediately after injury, acute blood loss leads to anemia, however, patients can remain anemic for as long as 6 months after injury. Research on the underlying mechanisms of such alterations of erythropoiesis after trauma has focused on the prolonged hypercatecholaminemia seen after trauma. Supraphysiologic elevation of catecholamines leads to an inhibitive effect on erythropoiesis. There is evidence to show that alleviation of the neuroendocrine stress response following trauma reduces these inhibitory effects. Both beta blockade and alpha-2 adrenergic receptor stimulation have demonstrated increased growth of hematopoietic progenitor cells as well as increased pro-erythropoietic cytokines after trauma. This review will describe prior research on the neuroendocrine stress response after trauma and its consequences on erythropoiesis, which offer insight into underlying mechanisms of prolonged anemia postinjury. We will then discuss the beneficial effects of adrenergic modulation to improve erythropoiesis following injury and propose future directions for the field.

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“…Prior studies have implicated systemic inflammation, disruption of iron homeostasis, prolonged HPC mobilization, hypercatecholaminemia, and chronic stress as contributors to bone marrow dysfunction after injury (6)(7)(8). Systemic inflammation that inhibits erythropoiesis is characterized by the presence of cytokines such as IL-1α, TNF-α, and interferon gamma (IFN-γ) (9)(10)(11)(12)(13)(14). Granulocyte colony-stimulating factor (G-CSF) is a known promoter of HPC mobilization, whereas C-X-C chemokine receptor type 4 (CXCR4), stromal cell-derived factor-1 (SDF-1; also known as C-X-C motif chemokine ligand 12 or CXCL12), and vascular cell adhesion protein 1 (VCAM-1) facilitate HPC retention in the bone marrow (15,16).…”

Section: Introductionmentioning

confidence: 99%

Effects of Trauma Plasma-Derived Exosomes on Hematopoietic Progenitor Cells

Munley

Kelly

Gillies

et al. 2023

Shock

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Background: Severe trauma disrupts bone marrow function resulting in persistent anemia and immunosuppression. Exosomes are extracellular vesicles implicated in disease, cellular functions, and immunomodulation. The effects of trauma plasma-derived exosomes on bone marrow hematopoiesis are unstudied; we hypothesized that trauma plasma-derived exosomes suppress bone marrow hematopoietic progenitor cell (HPC) growth and contribute to increased inflammatory cytokines and HPC mobilization. Methods: Plasma was collected from a prospective, cohort study of trauma patients (n = 15) with hip and/or femur fractures and an ISS > 15 and elective total hip arthroplasty (THA) patients (n = 15). Exosomes were isolated from both groups using the Invitrogen Total Exosome Isolation Kit. Healthy bone marrow was cultured with 2% plasma, 50 μg, 100 μg, or 200 μg of exosomal protein and HPC (granulocyte, erythrocyte, monocyte, megakaryocyte colony-forming units [CFU-GEMM], erythroid burst-forming units [BFU-E], and macrophage colony-forming units [CFU-GM]) growth assessed. After culturing healthy bone marrow stroma with 100 μg of exosomal protein, expression of cytokines and factors influencing HPC mobilization were assessed by qPCR. Differences were compared using the ANOVA, with significance defined as P < 0.05. Results: The only demographic difference was age; trauma patients were significantly younger than THA (mean 44 vs. 63 years). In vitro exposure to trauma plasma significantly decreased growth of all HPCs. In vitro exposure to 100 μg or 200 μg of trauma exosomal protein significantly decreased growth of BFU-E and CFU-GM, whereas 50 μg had no effect. Culture of trauma exosomal protein with bone marrow stromal cells resulted in increased expression of IFN-γ, IL-1α, TNF-α, G-CSF, CXCR4, SDF-1, and VCAM-1 in bone marrow stroma. Conclusions: Both plasma and plasma-derived exosomes from trauma patients adversely affect bone marrow function. Plasma-derived exosomes may contribute to altered hematopoiesis after severe trauma; analysis of exosomal content may improve our understanding of altered bone marrow function.

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Impact of Injury Severity on the Inflammatory State and Severe Anemia

Cited by 13 publications

References 38 publications

Physiologic risk factors for early acute kidney injury in severely injured patients

Physiologic risk factors for early acute kidney injury in severely injured patients

Adrenergic Modulation of Erythropoiesis After Trauma

Effects of Trauma Plasma-Derived Exosomes on Hematopoietic Progenitor Cells

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