Physical Exercise Induces Specific Adaptations Resulting in Reduced Organ Injury and Mortality During Severe Polymicrobial Sepsis

Soßdorf, Maik; Fischer, Jacqueline; Meyer, Stefan; Dahlke, Katja; Wissuwa, Bianka; Seidel, C.; Schrepper, Andrea; Bockmeyer, Clemens L.; Lupp, Amelie; Neugebauer, Sophie; Schmerler, Diana; Rödel, Jürgen; Claus, Ralf A.; Otto, Gordon P.

doi:10.1097/ccm.0b013e31828a2ae3

Cited by 32 publications

(32 citation statements)

References 41 publications

(38 reference statements)

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“…In line with other studies demonstrating an early increase in kidney damage markers in the PCI model [11,15,17,18], this study indicates that persistence of renal impairment can be observed at least up to 65 days after sepsis in a reliable percentage. Hereby, the intensity/duration of antibiotic rescue therapy might be predictive.…”

Section: Discussionsupporting

confidence: 91%

Impact of Antibiotic Treatment Intensity on Long-Term Sepsis-Associated Kidney Injury in a Polymicrobial Peritoneal Contamination and Infection Model

Otto¹,

Grünwald²,

Geis³

et al. 2015

Nephron

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Background/Aims: Long-term kidney affections after sepsis are poorly understood. Animal models for investigating kidney damage in the late phase of disease progression are limited. The aim of this study was to investigate the impact of two antibiotic regimes on persistence of kidney injury after peritonitis. Methods: Kidney damage was investigated 65 days after polymicrobial peritoneal contamination and infection (PCI) sepsis induction in C57BL/6 mice. Short-term antibiotic therapy (STA, 4 days) was compared to long-term (LTA, 10 days) treatment using plasma creatinine, plasma and urine neutrophil gelatinase-associated lipocalin (NGAL), urine albumin/creatinine ratio and renal histology. Results: Sepsis resulted in mortality rates of 68.2% (STA) and 61.0% (LTA). Surviving STA animals showed the most pronounced kidney damage indicated by significantly elevated levels of creatinine and acute tubular damage (ATD), whereas NGAL was significantly increased in LTA survivors only. A creatinine level above 0.3 mg/dl was used to define kidney injury, found in 21.4% of STA animals and 7.8% of LTA animals. While animals with kidney injury demonstrated significantly higher ATD scores and persistent tubular damage, no significant differences were found for plasma or urine NGAL levels or urine albumin/creatinine ratios. Conclusion: Prolonged antibiotic treatment reduced the rate of ongoing peritonitis-induced kidney injury in a C57BL/6 mouse model. Plasma or urine NGAL levels were not able to identify animals with or without persistent kidney injury. The kidney injury after the PCI mouse model represents prototypic clinical findings and should be used for further studies investigating disease mechanisms.

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Section: Discussionsupporting

confidence: 91%

Impact of Antibiotic Treatment Intensity on Long-Term Sepsis-Associated Kidney Injury in a Polymicrobial Peritoneal Contamination and Infection Model

Otto¹,

Grünwald²,

Geis³

et al. 2015

Nephron

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“…Allen et al (32) showed that exercise-induced modifications of gut microbiota altered intestinal responses to chemically induced colitis after fecal transplantation in gnotobiotic mice. Sossdorf et al (12) showed that exercise preconditioning reduced organ injury and increased survival by enhancing bacterial clearance in blood and organs and diminishing the release of pro-and anti-inflammatory cytokines in male C57BL/6N mice with polymicrobial sepsis. Al-Nassan and Fujino (14) showed that exercise preconditioning attenuated TNFainduced activation of atrophic mediators, including p38, FOXO3A, and multiubiquitin proteins, and preserved muscle mass in mice with LPS-induced sepsis.…”

Section: Discussionmentioning

confidence: 99%

“…Physical exercise has been reported to induce protection against inflammatory diseases (10,11). This protection has been reported in various animal models of sepsis and is associated with improving or modulating the host response to septic shock (12)(13)(14). In addition, recent animal studies indicate that exercise training may modulate gut microbiota-enhancing symbiosis (the provision of mutual benefits to both host and microbe).…”

mentioning

confidence: 96%

Exercise training modifies gut microbiota with attenuated host responses to sepsis in wild‐type mice

Kim

Kang

2019

FASEB j.

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This study investigated the effects of exercise preconditioning‐induced modification in gut microbiota composition and host responses to cecal ligation and puncture (CLP)‐induced sepsis. Four‐week‐old C57BL/6N male mice were randomly assigned to either CLP (n = 30) or CLP‐exercise (CLP+Exe; n = 30) groups. Prior to CLP‐induced sepsis, the CLP+Exe mice were subjected to 8 wk of treadmill running. Fecal samples were collected and analyzed by 16S rRNA amplification sequencing to assess gut microbiota composition. Diversity analyses such as principal coordinates analysis and rarefaction curves showed that exercise preconditioning was associated with differences in gut microbiota community structure and species richness. Exercise preconditioning‐induced differences in gut microbiota composition were also evident at the family level of taxonomic analysis, with the dominant phyla being Bacteriodetes, Firmicutes, Verrucomicrobia, and, to a lesser extent, Cyanobacteria. Compared with control mice, preconditioned mice had a higher survival rate and less organ damage during the acute phase of sepsis, secondary to attenuation of the host response to septic shock. The current findings suggest that exercise preconditioning‐induced modification in gut microbiota composition may lead to an attenuated host response to CLP‐induced sepsis in wild‐type mice, as shown by increased survival and less organ damage, as well as the establishment of a balance between pro‐ and anti‐inflammatory responses.—Kim, D., Kang, H. Exercise training modifies gut microbiota with attenuated host responses to sepsis in wild‐type mice. FASEB J. 33, 5772–5781 (2019). http://www.fasebj.org

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“…Sepsis is still the leading cause of death among critically ill patients in intensive care units. Furthermore, the survivors usually suffer from an impaired quality of life 1 2 3 4 5 6 . Administration of antibiotics against the known or experientially pathogens along with supportive care, which may help the patients survive acute stage of sepsis, frequently shift to a state of chronic morbidity lasting days to weeks 2 5 7 8 9 10 11 12 13 .…”

mentioning

confidence: 99%

Tuftsin-derived T-peptide prevents cellular immunosuppression and improves survival rate in septic mice

Gao

Chai

Dong

et al. 2015

Sci Rep

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The primary mechanisms of sepsis induced cellular immunesuppression involve immune dysfunction of T lymphocytes and negative immunoregulation of regulatory T cells (Tregs). It has been found that tuftsin is an immune modulating peptide derived from IgG in spleen. T-peptide is one of tuftsin analogs. Herein, we examined the effect of T-peptide on cell-mediated immunity in the presence of lipopolysaccharide (LPS) and the survival rate in septic mice. T-peptide regulated the proliferative ability of CD4+CD25− T cells in dual responses. Meanwhile, 10 and 100 μg/ml T-peptides were able to enhance the apoptotic rate of CD4+CD25− T cells compared with 1 μg/ml T-peptide, but markedly lowered interleukin (IL)-2 levels. When CD4+CD25+ Tregs were treated with T-peptide for 24 hours, and co-cultured with normal CD4+CD25− T cells, the suppressive ability of CD4+CD25+ Tregs on CD4+CD25− T cells was significantly lowered, along with decreased expression in forkhead/winged helix transcription factor p-3 (Foxp-3) as well as cytotoxic T lymphocyte-associated antigen (CTLA)-4, and secretion of transforming growth factor (TGF)-β. Moreover, T-peptide has the ability to improve outcome of septic mice in a dose- and time- dependent manner, and associated with improvement in the microenvironment of cellular immunosuppression in septic mice.

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Physical Exercise Induces Specific Adaptations Resulting in Reduced Organ Injury and Mortality During Severe Polymicrobial Sepsis

Abstract: Regular physical exercise reduces sepsis-associated acute kidney injury and death. As a specific mechanism of exercise-induced adaptation, we identified various lysophosphatidylcholines that might function as surrogate for improved outcome in sepsis.

Cited by 32 publications

References 41 publications

Impact of Antibiotic Treatment Intensity on Long-Term Sepsis-Associated Kidney Injury in a Polymicrobial Peritoneal Contamination and Infection Model

Impact of Antibiotic Treatment Intensity on Long-Term Sepsis-Associated Kidney Injury in a Polymicrobial Peritoneal Contamination and Infection Model

Exercise training modifies gut microbiota with attenuated host responses to sepsis in wild‐type mice

Tuftsin-derived T-peptide prevents cellular immunosuppression and improves survival rate in septic mice

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