Neutrophils in development of multiple organ failure in sepsis

Brown, K A; Brain, Susan D.; Jd, Pearson; Edgeworth, JD; Sm, Lewis; Treacher, D.F.

doi:10.1016/s0140-6736(06)69005-3

Cited by 575 publications

(563 citation statements)

References 155 publications

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“…The role of neutrophils in the development of multiple organ failure due to sepsis has been recently reviewed 6 . Perhaps what is of greater pathophysiological importance in causing severe sepsis is not the number of circulating neutrophils, but that these cells are not functionally active 25 .…”

Section: Discussionmentioning

confidence: 99%

Comparative study of survivor and nonsurvivor sepsis patients in a university hospital

Oliveira

Barata

Murta

et al. 2008

Rev. Soc. Bras. Med. Trop.

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To determine parameters associated with the evolution of sepsis, a five-year retrospective study was conducted in a university hospital. One hundred and four consecutive sepsis patients were evaluated, of whom 55.8% were men. The mortality was 68.3% and was associated with older age (p<0.05). Chronic comorbidities and infection site were not associated with prognosis. Gram-positive bacteria were more frequently identified in survivors (p<0.05), while non-detection of the germ was associated with mortality (p<0.01). Appropriate use of antibiotics (germ sensitive to at least one drug administered) was associated with survival (p<0.0001) while inappropriate use (p<0.05) or empirical use (p<0.01) were more frequent in nonsurvivors. Leukocytosis was the main abnormality (54.8%) detected on diagnosis, from the leukocyte count. During the evolution, normal leukocyte count was associated with survival (p<0.01) and leukocytosis with mortality (p<0.05). In conclusion, mortality was associated with nondetection of the pathogen, leukocytosis during the evolution of the sepsis and inappropriate or empirical use of antimicrobials. Evidence-based treatment that is directed towards modifiable risk factors might improve the prognosis for sepsis patients.Key-words: Sepsis. Prognosis. Antimicrobials. Risk factors. RESUMOPara determinar parâmetros associados à evolução da sepse, foi realizado estudo retrospectivo de 5 anos em um hospital universitário. Foram avaliados 104 pacientes consecutivos com sepse, sendo 55,8% homens. A mortalidade foi de 68,3%, associada à idade elevada (p<0,05). Doenças crônicas associadas e sítio de infecção não relacionados ao prognóstico. Identificação de bactérias Gram-positivos foi mais frequente em sobreviventes (p<0,05) e não detecção do germe foi associada à mortalidade (p<0,01). O uso apropriado de antibióticos (germe sensível a pelo menos uma droga administrada) foi associado à sobrevida (p<0,0001) enquanto uso inapropriado (p<0,05) ou empírico (p<0,01) foi mais freqüente em não sobreviventes. No diagnóstico, leucocitose foi a principal (54,8%) alteração no leucograma. Na evolução, leucograma normal foi associado à sobrevida (p<0,01) e leucocitose à mortalidade (p<0,05). Em conclusão, a mortalidade foi associada à ausência de detecção do germe, leucocitose na evolução da sepse e uso inapropriado ou empírico de antibióticos. O tratamento baseado em evidências e direcionado para fatores de risco que podem ser modificados deve melhorar o prognóstico do paciente com sepse.Palavras-chaves: Sepse. Prognóstico. Antimicrobianos. Fatores de risco.Fatores de risco.

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Section: Discussionmentioning

confidence: 99%

Comparative study of survivor and nonsurvivor sepsis patients in a university hospital

Oliveira

Barata

Murta

et al. 2008

Rev. Soc. Bras. Med. Trop.

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“…Total RNA from peritoneal exudate cells (PEC) 3 at each point was extracted using TRIzol reagent (Invitrogen Life Technologies). The firststranded cDNA synthesis was done using Superscript I (Invitrogen Life Technologies), according to manufacturer's instruction.…”

Section: Rna Isolation Cdna Synthesis and Real-time Pcrmentioning

confidence: 99%

“…Under normal conditions, neutrophils are hardly found in peripheral tissues, but are abundant in the blood (3). After pathogens enter the body through the outer physical barriers, neutrophils are the first to infiltrate the site of infection.…”

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confidence: 99%

Resident Vδ1+ γδ T Cells Control Early Infiltration of Neutrophils after Escherichia coli Infection via IL-17 Production

Shibata

Yamada

Hara

et al. 2007

The Journal of Immunology

440

410

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Neutrophils infiltrate the site of infection and play critical roles in host defense, especially against extracellular bacteria. In the present study, we found a rapid and transient production of IL-17 after i.p. infection with Escherichia coli, preceding the influx of neutrophils. Neutralization of IL-17 resulted in a reduced infiltration of neutrophils and an impaired bacterial clearance. Ex vivo intracellular cytokine flow cytometric analysis revealed that γδ T cell population was the major source of IL-17. Mice depleted of γδ T cells by mAb treatment or mice genetically lacking Vδ1 showed diminished IL-17 production and reduced neutrophil infiltration after E. coli infection, indicating an importance of Vδ1+ γδ T cells as the source of IL-17. It was further revealed that γδ T cells in the peritoneal cavity of naive mice produced IL-17 in response to IL-23, which was induced rapidly after E. coli infection in a TLR4 signaling-dependent manner. Thus, although γδ T cells are generally regarded as a part of early induced immune responses, which bridge innate and adaptive immune responses, our study demonstrated a novel role of γδ T cells as a first line of host defense controlling neutrophil-mediated innate immune responses.

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“…Although killing of microorganisms is apparently a beneficial function of neutrophil activation, exaggerated activation of neutrophils can result in collateral damage to tissues and also contribute to the development of organ failure in sepsis (9,10). However, impairment of neutrophil activation also can lead to serious complications in infected patients.…”

Section: Introductionmentioning

confidence: 99%

Activation of AMPK Enhances Neutrophil Chemotaxis and Bacterial Killing

Park

Jiang

Tadié

et al. 2013

Mol Med

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An inability of neutrophils to eliminate invading microorganisms is frequently associated with severe infection and may contribute to the high mortality rates associated with sepsis. In the present studies, we examined whether metformin and other 5′ adenosine monophosphate-activated protein kinase (AMPK) activators affect neutrophil motility, phagocytosis and bacterial killing. We found that activation of AMPK enhanced neutrophil chemotaxis in vitro and in vivo, and also counteracted the inhibition of chemotaxis induced by exposure of neutrophils to lipopolysaccharide (LPS). In contrast, small interfering RNA (siRNA)-mediated knockdown of AMPKα1 or blockade of AMPK activation through treatment of neutrophils with the AMPK inhibitor compound C diminished neutrophil chemotaxis. In addition to their effects on chemotaxis, treatment of neutrophils with metformin or aminoimidazole carboxamide ribonucleotide (AICAR) improved phagocytosis and bacterial killing, including more efficient eradication of bacteria in a mouse model of peritonitis-induced sepsis. Immunocytochemistry showed that, in contrast to LPS, metformin or AICAR induced robust actin polymerization and distinct formation of neutrophil leading edges. Although LPS diminished AMPK phosphorylation, metformin or AICAR was able to partially decrease the effects of LPS/toll-like receptor 4 (TLR4) engagement on downstream signaling events, particularly LPS-induced IκBα degradation. The IκB kinase (IKK) inhibitor PS-1145 diminished IκBα degradation and also prevented LPS-induced inhibition of chemotaxis. These results suggest that AMPK activation with clinically approved agents, such as metformin, may facilitate bacterial eradication in sepsis and other inflammatory conditions associated with inhibition of neutrophil activation and chemotaxis. Online address: https://doi.org/www.molmed.org

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Neutrophils in development of multiple organ failure in sepsis

Cited by 575 publications

References 155 publications

Comparative study of survivor and nonsurvivor sepsis patients in a university hospital

Comparative study of survivor and nonsurvivor sepsis patients in a university hospital

Resident Vδ1+ γδ T Cells Control Early Infiltration of Neutrophils after Escherichia coli Infection via IL-17 Production

Activation of AMPK Enhances Neutrophil Chemotaxis and Bacterial Killing

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