Innate Immune Responses in Swine Resuscitated from Severe Traumatic Hemorrhagic Shock with Hemoglobin-Based Oxygen Carrier-201

Abstract

Hemoglobin-based oxygen carrier-201 transports oxygen and improves survival in swine with hemorrhagic shock, but has potential to be immune activating. Herein, we evaluated HBOC-201's immune effects in swine with more severe hemorrhagic shock due to soft tissue injury and 55% blood volume catheter withdrawal over 15 minutes followed by fluid resuscitation at 20 minutes with HBOC-201, Hextend, or no treatment (NON) before hospital arrival. Survival rates were similar with HBOC-201 and Hextend (p > 0.05), but were higher than in (p = 0.007). There were no significant group differences in blood cell count, percentages of leukocyte sub-populations and immunophenotype (CD4:CD8 ratio), adhesion markers expression (neutrophil CD11b; monocyte or neutrophil CD49d) and apoptosis. There was a trend to higher plasma IL-10 in HBOC-201 and groups vs. Hextend. We conclude that in swine with severe controlled HS and soft tissue injury, immune responses are similar with resuscitation with HBOC-201 and Hextend.

Immune Safety Evaluation of Polymerized Porcine Hemoglobin (pPolyHb): A Potential Red Blood Cell Substitute

“…To the contrary, it may help to attenuate the existing inflammatory symptom. Similar results were also seen in a swine model of HBOC-201, which showed that HBOC-201 had no significant adverse or beneficial effects on immune function in a swine model of moderately severe HS and severe controlled HS [14][15][16]. Our in vitro results are consistent with in vivo results in that there is no inflammatory reaction caused by addition or infusion of pPolyHb.…”

“…Ortegon et al observed that HBOC-201 had immune-activating potential, especially enhancement of neutrophilic β 2 integrin (CD11b) expression at high concentration in vitro [13]. However, in vivo in moderate and severe controlled hemorrhagic shock (HS) in swine, with the exception of mildly increased plasma levels of the anti-inflammatory Th-2 cytokine, IL-10, HBOC-201 had minimal effects on innate immune responses [14][15][16]. As well, in trauma patients human polymerized hemoglobin (Polyheme) diminished immune activation in comparison with blood transfusions [17].…”

Conjugation of Hemoglobin and Mannan Markedly Improves the Immunogenicity of Domain III of the Zika Virus E Protein: Structural and Immunological Study

“…Hb and mannan both functioned as the adjuvants. As an oxygen carrier, Hb was a potential immunomodulatory protein without a significant adverse immune effect, which could regulate inflammation, cytokine secretion, and activation of macrophage in the plasma. , Mannan was a ligand of TLR-4 or TLR-2 and could be recognized via mannose receptor, dectin-2, and DC-SIGN, which induce Th1-type and Th2-type immune response. − Hb and mannan could play the immunomodulatory activities in a synergistic manner. Consistently, physical administration of HM with EDIII was demonstrated to increase the immunogenicity of EDIII in the present study.…”

Experimental Models of Hemorrhagic Shock: A Review

“…According to Advanced Trauma Life Support, if the bleeding rate exceeds 40% of circulating blood volume (class IV), the mortality rate is more than 30% in the clinical scenario [19]. Most investigators attempt to recreate this level of shock [12,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49](table 2). …”