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Endotoxin Tolerance Drives Neutrophil To Infectious Site

Ariga, Suely Kubo; Abatepaulo, Fátima Bernardes; Melo, Edielle Sant Anna; Velasco, Irineu Tadeu; da Silva, Fabiano Pinheiro; de Lima, Thais Martins; Soriano, Francisco Garcia

doi: 10.1097/SHK.0000000000000175
Basic Science Aspects

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.

Emergency Medicine Department, Medical School, University of São Paulo, São Paulo, Brazil

Received 27 Dec 2013; first review completed 16 Jan 2014; accepted in final form 11 Mar 2014

Address correspondence to Francisco Garcia Soriano, MD, PhD, Laboratório da Disciplina de Emergências Clínicas, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo 455, sala 3187, 01246-913, São Paulo, Brazil. E-mail:

The authors have no conflicts of interest to declare.

This study was supported by grants FAPESP-02/07430-6 and CNPq-470744/2004-9.

© 2014 by the Shock Society