Body temperature and mouse scoring systems as surrogate markers of death in cecal ligation and puncture sepsis

Safiah, H. C.; Sharma, Neha; Kwong, Andrew C; Dwivedi, Dhruva J.; Khan, Momina; Grin, Peter M.; Fox‐Robichaud, Alison; Liaw, Patricia C.

doi:10.1186/s40635-018-0184-3

Cited by 89 publications

(92 citation statements)

References 30 publications

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“…Strong differences among compartments are likely 67 and the blood compartment constitutes only a small representation of the entire immuno-inflammatory status of the host. Our results strongly indicate that accompanying survival studies (or using a reliable death surrogates 68 , 69 ) should be viewed as an important validation step in 2-hit modeling systems. Lack of such a verification may lead to misleading results from which inappropriate conclusions are drawn.…”

Section: Discussionmentioning

confidence: 64%

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

Drechsler

Zipperle

Rademann

et al. 2018

Sci Rep

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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 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 1st hit solely based on the common immuno-inflammatory parameters could be misleading.

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Section: Discussionmentioning

confidence: 64%

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

Drechsler

Zipperle

Rademann

et al. 2018

Sci Rep

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“…Decreased cardiac output and blood pressure may be associated with hypothermia (Fig. 1c) [11,37], reinforcing the need to measure body temperature in sepsis mice models.…”

Section: Discussionmentioning

confidence: 98%

“…In our study, these neurological effects were re ected in the impairment of the level of consciousness and activity in the Sepsis group ( Figure S1a,c). The neurological symptoms can be identi ed in the rst hours by MSS [11], but using the A-MSS allows the assessment of autonomic insu ciency evaluating the temperature (Fig. 1c).…”

Section: Discussionmentioning

confidence: 99%

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Adapted Murine Sepsis Score: Improving The Research In Experimental Sepsis Mice Model

Sulzbacher

Passos

et al. 2020

Preprint

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Objective The Murine Sepsis Score (MSS) is used to assess the severity of sepsis in rats and mice based on observational characteristics. The quantitative variables of blood glucose, body weight and temperature are predictors of severity in experimental models of sepsis. Therefore, our study sought to adapt the MSS with the same variables to indicate earlier the severity of the disease in murine models of the disease. Results Sepsis mice presented hypoglycemia, weight loss, and hypothermia. Therefore, these variables were included in the Adapted Murine Sepsis Score (A-MSS). The A-MASS presented 100% specificity and 87.5% sensibility been able to differentiate the early sepsis symptoms and its severity. The A-MSS allows an early and more complete diagnosis of sepsis in mice and might be considered as a procedure to improve the analysis of systemic sepsis dysfunction in murine experimental models.

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“…The scoring indicated that the mice infected with the steA strain probably died of a heightened immune response. We also checked the body temperatures of mice infected with 5 × 10 5 wt, steA, and compl and found lower body temperatures of steAinfected mice, indicating that probably mice were undergoing sepsis (35).…”

Section: Stea Affects the Pathogenesis Of Salmonella Typhimuriummentioning

confidence: 98%

Salmonella Effector SteA Suppresses Proinflammatory Responses of the Host by Interfering With IκB Degradation

2019

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Salmonella enterica serovar Typhimurium is known to cause its virulence by secreting various effector proteins directly into the host cytoplasm via two distinct type III secretion systems (T3SS-1 and T3SS-2). Generally, T3SS-1-delivered effectors help Salmonella Typhimurium in the early phases of infection including invasion and immune modulation of the host cells, whereas T3SS-2 effectors mainly help in the survival of Salmonella Typhimurium within the host cells including maintenance of Salmonella-containing vacuole, replication of the bacteria, and dissemination. Some of the effectors are secreted via both T3SS-1 and T3SS-2, suggesting their role in distinct phases of infection of host cells. SteA is such an effector that is secreted by both T3SS-1 and T3SS-2. It has been shown to control the membrane dynamics of the Salmonella-containing vacuole within the host cells in the late phases of infection. In this manuscript, toward characterizing the T3SS-1 function of SteA, we found that SteA suppresses inflammatory responses of the host by interfering with the nuclear factor kappa B pathway. Our initial observation showed that the mice infected with steA-deleted Salmonella Typhimurium (steA) died earlier compared to the wild-type bacteria due to heightened immune responses, which indicated that SteA might suppress immune responses. Furthermore, our study revealed that SteA suppresses immune responses in macrophages by interfering with the degradation of IκB, the inhibitor of nuclear factor kappa B. SteA suppresses the ubiquitination and hence degradation of IκB by acting on Cullin-1 of the Skp-1, Cullin-1, F-box (SCF)-E3 ligase complex. Our study revealed that SteA suppresses a key step necessary for E3 ligase activation, i.e., neddylation of Cullin-1 by interfering with dissociation of its inhibitor Cand-1.

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Body temperature and mouse scoring systems as surrogate markers of death in cecal ligation and puncture sepsis

Cited by 89 publications

References 30 publications

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

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

Adapted Murine Sepsis Score: Improving The Research In Experimental Sepsis Mice Model

Salmonella Effector SteA Suppresses Proinflammatory Responses of the Host by Interfering With IκB Degradation

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