Endotoxin Tolerance Drives Neutrophil To Infectious Site

Abstract

The objective of this randomized animal study and laboratory investigation was to investigate whether lipopolysaccharide tolerance redirects neutrophil migration between organs. Male BALB/c mice received subcutaneous injections of lipopolysaccharide (1 mg/kg) for 5 days, followed by cecal ligation and puncture (CLP). Cytokines and adhesion molecules were measured after tolerance and CLP challenge. Increased numbers of neutrophils were observed in the peritoneal cavity of tolerant mice, which was associated with increased levels of adhesion molecules and chemokines. In contrast, nontolerant mice accumulated higher numbers of neutrophils in the lungs compared with those in the peritoneal cavity. Neutrophil function accessed by hydrogen peroxide production from neutrophils recovered from peritoneal cavity showed that tolerance increased the capacity to produce hydrogen peroxide. Mortality was reduced in tolerant animals. This study demonstrated that tolerance reduces leukocyte accumulation in the lung after CLP by redirecting neutrophils to the site of infection.

NFκB2/p100 Is a Key Factor for Endotoxin Tolerance in Human Monocytes: A Demonstration Using Primary Human Monocytes from Patients with Sepsis

“…Therefore, tolerant monocytes might recruit phagocytic cells to the infection site for resolution, opening new avenues of research in this field. Similar results have been reported in an in vivo model of ET, in which neutrophils were preferentially recruited by tolerant monocytes (39). In contrast, after siRp100 transfection in both tolerant and septic monocytes, the levels of CCL2 and CCL18 were found to be significantly downregulated.…”

What’s New in Shock, August 2014?

“…To conclude the sepsis-themed marathon, Ariga et al (13) show mice primed with LPS before induction of sepsis by CLP display an advantageous outlook in survival compared with the control groups. Also known as Bendotoxin tolerance,[ mice receiving continuous subcutaneous LPS challenge (5 days) followed by CLP express higher levels of adhesion molecules in the peritoneum compared with the control group.…”

Estudo sobre a produção e a ação dos peptídeos antimicrobianos em camundongos submetidos à tolerância ao LPS e à sepse por ligadura e punção cecal

“…Estudos mostraram que existe uma assinatura gênica de tolerância que está associada à piora no prognóstico dos pacientes (Hotckiss et al, 2013;Pena et al, 2014;Davenport et al, 2016) (Lehner et al, 2001;Romero et al, 2011;Murphey et al, 2011;Ariga 2014).…”

“…A indução de tolerância normalmente reduz a produção de mediadores que sustentam ou amplificam a inflamação (por exemplo: TNF-α, IL-1β), contudo mantem a capacidade do organismo em fagocitar e combater bactérias e outros agentes invasores (Ariga et al 2014, De Lima 2014. Nossos resultados plasmáticos mostram uma resposta aumentada da β defensina-3 e do CRAMP no grupo tolerante submetido à CLP, sugerindo que uma maior concentração de AMPs também auxiliaria na capacidade de eliminação de bactérias (Figura 5).…”

“…No entanto, a tolerância diminuiu a concentração de TNF-α no tecido, evidenciando um efeito anti-inflamatório e, consequentemente protetor, da tolerância no pulmão dos animais (Figuras 7 e 10 A).Nosso grupo demonstrou recentemente esse efeito anti-inflamatório da tolerância no pulmão de animais submetidos à CLP (Ariga et al, 2014). Neste estudo também mostramos a menor migração de leucócitos para o pulmão dos animais devido à modulação da expressão de moléculas de adesão.…”