Hypertonic saline solution drives neutrophil from bystander organ to infectious site in polymicrobial sepsis: a cecal ligation and puncture model.
The effects of hypertonic saline solution (HSS) have been shown in several animal models of ischemia and shock. Literature has shown potential benefits of HSS modulating inflammatory response after sepsis in an animal model. We studied the HSS effects in sepsis through cecal ligation and puncture (CLP) in Balb-C mice. Groups studied: 1- CLP without treatment (CLP-C); 2- CLP treated with normal saline solution NaCl 0.9% - 34 ml/Kg (CLP-S); 3- CLP treated with HSS NaCl 7.5% - 4 ml/Kg (CLP-H); and 4- group (Basal) without no CLP or treatment. Volume infusion was always applied 30 min after CLP. Lung and peritoneal lavage were harvested after 6h and 24h of CLP to analyze cytokines amount, oxide nitric, lipid peroxidation and neutrophil infiltration. Neutrophil infiltration, ICAM-1, CXCR-2, and CXCL-1 in lung were reduced by HSS (CLP-H) compared to CLP-C or CLP-S. Neutrophil in peritoneal lavage was increased in 24h with HSS (CLP-H) compared to CLP and CLP-S. Peritoneal CXCR-2 was increased in CLP-C and CLP-S but presented a lower increase with HSS (CLP-H) after 6 hours. GRK-2 presented difference among the groups at 24 h, showing a profile similar to neutrophil infiltration. Pro-inflammatory cytokines (TNF-α and IL-6) were reduced by HSS treatment; CLP-S increased TNF-α. IL-10 was increased in lung tissue by the HSS treatment. The oxidative stress (TBARS and nitric oxide biochemistry markers) was reduced with HSS. Animal survival was 33.3% in CLP-C group, 46.6% in CLP-S group and 60% in the CLP-H group after the sixth day. The HSS protects the animal against sepsis. Our results suggest that the volume replacement modulate pro and anti-inflammatory mediators of an inflammatory response, but HSS presented a more effective and potent effect.
Emergency of Medicine Division-Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Mariana Cardillo
MC
Theobaldo
Flavia
F
Llimona
Ricardo Costa
RC
Petroni
Ester Correia Sarmento
EC
Rios
Irineu Tadeu
IT
Velasco
Francisco Garcia
FG
Soriano
D000818:Animals; D054360:Chemokine CXCL1 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects* / Q000276:immunology; D018384:Oxidative Stress; D010529:Peritoneal Cavity / Q000473:pathology; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage*; D018805:Sepsis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D054360:Chemokine CXCL1; D016207:Cytokines; D023063:Receptors, Interleukin-8B; D012462:Saline Solution, Hypertonic; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D054769:G-Protein-Coupled Receptor Kinase 2