Dataset Information

Splenectomy modulates early immuno-inflammatory responses to trauma-hemorrhage and protects mice against secondary sepsis.

ABSTRACT: In polytrauma patients, the impact of splenectomy is equivocal, ranging from negative to protective. We investigated the impact of splenectomy on immune responses in the 1^st-hit polytrauma alone and on survival in the post-traumatic sepsis (2^nd hit). Female BALB/c mice underwent polytrauma (1^st hit) consisting of either a) TH: femur fracture, hemorrhagic shock or b) TSH: splenectomy, femur fracture, hemorrhagic shock. Additionally, the polytrauma hit was followed by cecal ligation and puncture (CLP) 48 h later and compared to CLP alone. Splenectomy improved the 28-day survival in secondary sepsis to 92% (from 62%), while TH lowered it to 46% (p < 0.05). The improved survival was concurrent with lower release of inflammatory cytokines (IL-6, CXCL-1, MCP-1) and increase of C5a post-CLP. In the polytrauma hit alone, TSH induced stronger neutrophilia (1.9 fold) and lymphocytosis (1.7 fold) when compared to TH mice. Moreover, TSH resulted in a 41% rise of regulatory T-cells and reduced the median fluorescence intensity of MHC-2 on monocytes by 55% within 48 h (p < 0.05). Conversely, leukocyte phagocytic capacity was significantly increased by 4-fold after TSH despite a similar M1/M2 macrophage profile in both groups. Summarizing, splenectomy provoked both immuno-suppressive and immuno-stimulatory responses but was life-saving in secondary sepsis. Additionally, the polytrauma components in 2-hit models should be tested for their effects on outcome; the presumed end-effect of the 1^st hit solely based on the common immuno-inflammatory parameters could be misleading.

SUBMITTER: Drechsler S

PROVIDER: S-EPMC6173732 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Splenectomy modulates early immuno-inflammatory responses to trauma-hemorrhage and protects mice against secondary sepsis.

Drechsler S S Zipperle J J Rademann P P Jafarmadar M M Klotz A A Bahrami S S Osuchowski M F MF

Scientific reports 20181005 1

In polytrauma patients, the impact of splenectomy is equivocal, ranging from negative to protective. We investigated the impact of splenectomy on immune responses in the 1st-hit polytrauma alone and on survival in the post-traumatic sepsis (2nd hit). Female BALB/c mice underwent polytrauma (1st hit) consisting of either a) TH: femur fracture, hemorrhagic shock or b) TSH: splenectomy, femur fracture, hemorrhagic shock. Additionally, the polytrauma hit was followed ...[more]

PMID: 30291296

Similar Datasets

Project description:BackgroundDespite many animal studies and clinical trials, mortality in sepsis remains high. This may be due to the fact that most experimental studies of sepsis employ young animals, whereas the majority of septic patients are elderly (60?-?70 years). The objective of the present study was to examine the sepsis-induced inflammatory and pro-coagulant responses in aged mice. Since running exercise protects against a variety of diseases, we also examined the effect of voluntary running on septic responses in aged mice.MethodsMale C57BL/6 mice were housed in our institute from 2-3 to 22 months (an age mimicking that of the elderly). Mice were prevented from becoming obese by food restriction (given 70-90% of ad libitum consumption amount). Between 20 and 22 months, a subgroup of mice ran voluntarily on wheels, alternating 1-3 days of running with 1-2 days of rest. At 22 months, mice were intraperitoneally injected with sterile saline (control) or 3.75 g/kg fecal slurry (septic). At 7 h post injection, we examined (1) neutrophil influx in the lung and liver by measuring myeloperoxidase and/or neutrophil elastase in the tissue homogenates by spectrophotometry, (2) interleukin 6 (IL6) and KC in the lung lavage by ELISA, (3) pulmonary surfactant function by measuring percentage of large aggregates, (4) capillary plugging (pro-coagulant response) in skeletal muscle by intravital microscopy, (5) endothelial nitric oxide synthase (eNOS) protein in skeletal muscle (eNOS-derived NO is putative inhibitor of capillary plugging) by immunoblotting, and (6) systemic blood platelet counts by hemocytometry.ResultsSepsis caused high levels of pulmonary myeloperoxidase, elastase, IL6, KC, liver myeloperoxidase, and capillary plugging. Sepsis also caused low levels of surfactant function and platelet counts. Running exercise increased eNOS protein and attenuated the septic responses.ConclusionsVoluntary running protects against exacerbated sepsis-induced inflammatory and pro-coagulant responses in aged mice. Protection against pro-coagulant responses may involve eNOS upregulation. The present discovery in aged mice calls for clinical investigation into potential beneficial effects of exercise on septic outcomes in the elderly.

Project description:Although physiological responses to hemorrhage are well-studied, hemorrhage is often accompanied by trauma, and it remains unclear how injury affects these responses. This study examined effects of extremity trauma on cardiorespiratory responses and survival to moderate (37%; H-37) or severe (50%; H-50) hemorrhage in rats. Transmitter and carotid catheter implantation and extremity trauma (fibular fracture and muscle injury) were conducted 2 wk, 24 h, and 90 min, respectively, before conscious hemorrhage. Mean arterial pressure (MAP) and heart rate (HR; via telemetry), and respiration rate (RR), minute volume (MV), and tidal volume (TV; via plethysmography) were measured throughout the 25 min hemorrhage and remainder of the 4 h observation period. There were four groups: 1) H-37, no trauma (NT; n = 17); 2) H-37, extremity trauma (T, n = 18); 3) H-50, NT (n = 20); and 4) H-50, T (n = 20). For H-37, during and after hemorrhage, T increased HR (P ≤ 0.031) and MV (P ≤ 0.048) compared with NT rats. During H-50, T increased HR (0.041) and MV (P = 0.043). After hemorrhage, T increased MV (P = 0.008) but decreased HR (P = 0.007) and MAP (P = 0.039). All cardiorespiratory differences between T and NT groups were intermittent. Importantly, both survival time (159.8 ± 78.2 min vs. 211.9 ± 60.3 min; P = 0.022; mean ± SD) and percent survival (45% vs. 80%; P = 0.048) were less in T versus NT rats after H-50. Trauma interacts with physiological systems in a complex manner and no single cardiorespiratory measure was sufficiently altered to indicate that it alone could account for increased mortality after H-50.NEW & NOTEWORTHY In both civilian and military settings, severe hemorrhage rarely occurs in the absence of tissue trauma, yet many animal models for the study of hemorrhage do not include significant tissue trauma. This study using conscious unrestrained rats clearly demonstrates that extremity trauma worsens the probability of survival after a severe hemorrhage. Although no single cardiorespiratory factor accounted for the increased mortality, multiple modest time-related cardiorespiratory responses to the trauma were observed suggesting that their combined dysfunction may have contributed to the reduced survival.

Project description:ObjectiveThe purpose of this study was to identify a panel of biomarkers for distinguishing early stage sepsis patients from non-infected trauma patients.BackgroundAccurate differentiation between trauma-induced sterile inflammation and real infective sepsis poses a complex life-threatening medical challenge because of their common symptoms albeit diverging clinical implications, namely different therapies. The timely and accurate identification of sepsis in trauma patients is therefore vital to ensure prompt and tailored medical interventions (provision of adequate antimicrobial agents and if possible eradication of infective foci) that can ultimately lead to improved therapeutic management and patient outcome. The adequate withholding of antimicrobials in trauma patients without sepsis is also important in aspects of both patient and environmental perspective.MethodsIn this proof-of-concept study, we employed advanced technologies, including Matrix-Assisted Laser Desorption/Ionization (MALDI) and multiplex antibody arrays (MAA) to identify a panel of biomarkers distinguishing actual sepsis from trauma-induced sterile inflammation.ResultsBy comparing patient groups (controls, infected and non-infected trauma and septic shock patients under mechanical ventilation) at different time points, we uncovered distinct protein patterns associated with early trauma-induced sterile inflammation on the one hand and sepsis on the other hand. SYT13 and IL1F10 emerged as potential early sepsis biomarkers, while reduced levels of A2M were indicative of both trauma-induced inflammation and sepsis conditions. Additionally, higher levels of TREM1 were associated at a later stage in trauma patients. Furthermore, enrichment analyses revealed differences in the inflammatory response between trauma-induced inflammation and sepsis, with proteins related to complement and coagulation cascades being elevated whereas proteins relevant to focal adhesion were diminished in sepsis.ConclusionsOur findings, therefore, suggest that a combination of biomarkers is needed for the development of novel diagnostic approaches deciphering trauma-induced sterile inflammation from actual infective sepsis.

Dataset Information

Splenectomy modulates early immuno-inflammatory responses to trauma-hemorrhage and protects mice against secondary sepsis.

Publications

Splenectomy modulates early immuno-inflammatory responses to trauma-hemorrhage and protects mice against secondary sepsis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets