title: Pre-treatment with low-dose endotoxin prolongs survival from experimental lethal endotoxic shock: Benefit for lethal peritonitis by Escherichia coli.
abstract: Although LPS tolerance is well-characterized, it remains unknown if it is achieved even with single doses of lipopolysaccharide (LPS) and if it offers protection against lethal bacterial infections. To this end, C57B6 mice were assigned to groups A (sham); B (saline i.p followed after 24h by i.p 30mg/kg LPS); and C (3mg/kg LPS i.p followed after 24h by i.p 30mg/kg LPS). Survival was monitored and animals were sacrificed early after lethal challenge for measurement of tumour necrosis factor-alpha (TNFα) in serum; isolation of splenocytes and cytokine stimulation; and flow-cytometry for apoptosis and TREM-1. Experiments were repeated with mice infected i.p by Escherichia coli after challenging with saline or LPS. Mortality of group B was 72.2% compared with 38.9% of group C (p: 0.020). Serum TNFα of group C was lower than group B. Expression of TREM-1 of group C on monocytes/neutrophils was greater than group B. Release of TNFα, of IFNγ and of IL-17 from splenocytes of group C was lower than group B and the opposite happened for IL-10 showing evidence of cellular reprogramming. In parallel, apoptosis of circulating lymphocytes and of splenocytes of group C was greater compared with group B. Pre-treatment of mice challenged by E. coli with low dose LPS led to 0% mortality compared with 90% of saline pre-treated mice; in these mice, splenocytes improved over-time their capacity for release of IFNγ. It is concluded that single low doses of LPS lead to early reprogramming of the innate immune response and prolong survival after lethal E. coli challenge.
authors.affiliation: 3rd Department of Surgery, University of Athens, Medical School, Greece. kkopanakis@gmail.com
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kopanakis
authors.forename: Ira-Maria
authors.initials: IM
authors.lastname: Tzepi
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Pistiki
authors.forename: Dionyssia-Pinelopi
authors.initials: DP
authors.lastname: Carrer
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Marianna
authors.initials: M
authors.lastname: Georgitsi
authors.forename: Maria
authors.initials: M
authors.lastname: Lymperi
authors.forename: Dionyssia-Irini
authors.initials: DI
authors.lastname: Droggiti
authors.forename: Theodoros
authors.initials: T
authors.lastname: Liakakos
authors.forename: Anastasios
authors.initials: A
authors.lastname: Machairas
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
mesh_terms: D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000097:blood; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000382:microbiology / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008070:Lipopolysaccharides; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000097:blood / Q000139:chemically induced / Q000382:microbiology* / Q000473:pathology*; D011971:Receptors, Immunologic / Q000378:metabolism; D012772:Shock, Septic / Q000097:blood / Q000139:chemically induced* / Q000473:pathology*; D013154:Spleen / Q000473:pathology; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C517262:TREM1 protein, mouse; D000073871:Triggering Receptor Expressed on Myeloid Cells-1