title: Therapeutic Effects of Treatment with Anti-TLR2 and Anti-TLR4 Monoclonal Antibodies in Polymicrobial Sepsis.
abstract: BACKGROUND
  Toll-like receptors (TLRs) play an important role in the recognition of microbial products and in host defense against infection. However, the massive release of inflammatory mediators into the bloodstream following TLR activation following sepsis is thought to contribute to disease pathogenesis.
  
  
  METHODS
  Here, we evaluated the effects of preventive or therapeutic administration of monoclonal antibodies (mAbs) targeting either TLR2 or TLR4 in a model of severe polymicrobial sepsis induced by cecal ligation and puncture in mice.
  
  
  RESULTS
  Pre-treatment with anti-TLR2 or anti-TLR4 mAb alone showed significant protection from sepsis-associated death. Protective effects were observed even when the administration of either anti-TLR2 or anti-TLR4 alone was delayed (i.e., 3 h after sepsis induction). Delayed administration of either mAb in combination with antibiotics resulted in additive protection.
  
  
  CONCLUSIONS
  Although attempts to translate preclinical findings to clinical sepsis have failed so far, our preclinical experiments strongly suggest that there is a sufficient therapeutic window within which patients with ongoing sepsis could benefit from combined antibiotic plus anti-TLR2 or anti-TLR4 mAb treatment.
authors.affiliation: Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena 190, sala 203, 30130-100, Belo Horizonte, MG, Brasil.
authors.forename: Cristiano Xavier
authors.initials: CX
authors.lastname: Lima
authors.affiliation: Instituto de Ciências Biologicas, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brasil.
authors.forename: Danielle Gloria
authors.initials: DG
authors.lastname: Souza
authors.affiliation: Instituto de Ciências Biologicas, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brasil.
authors.forename: Flavio Almeida
authors.initials: FA
authors.lastname: Amaral
authors.affiliation: Instituto de Ciências Biologicas, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brasil.
authors.forename: Caio Tavares
authors.initials: CT
authors.lastname: Fagundes
authors.affiliation: Instituto de Ciências Biologicas, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brasil.
authors.forename: Irla Paula Stopa
authors.initials: IP
authors.lastname: Rodrigues
authors.affiliation: Faculdade de Medicina de Ribeirão Preto, USP Avenida dos Bandeirantes, 3.900, Monte Alegre, 14049-900, Ribeirão Preto, SP, Brasil.
authors.forename: Jose Carlos
authors.initials: JC
authors.lastname: Alves-Filho
authors.affiliation: NovImmune SA, 14 Chemin des Aulx, 1228 Plan-Les-Ouates, Geneva, CH1228, Switzerland.
authors.forename: Marie
authors.initials: M
authors.lastname: Kosco-Vilbois
authors.affiliation: NovImmune SA, 14 Chemin des Aulx, 1228 Plan-Les-Ouates, Geneva, CH1228, Switzerland.
authors.forename: Walter
authors.initials: W
authors.lastname: Ferlin
authors.affiliation: NovImmune SA, 14 Chemin des Aulx, 1228 Plan-Les-Ouates, Geneva, CH1228, Switzerland.
authors.forename: Limin
authors.initials: L
authors.lastname: Shang
authors.affiliation: NovImmune SA, 14 Chemin des Aulx, 1228 Plan-Les-Ouates, Geneva, CH1228, Switzerland.
authors.forename: Greg
authors.initials: G
authors.lastname: Elson
authors.affiliation: Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena 190, sala 203, 30130-100, Belo Horizonte, MG, Brasil; Instituto de Ciências Biologicas, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brasil.
authors.forename: Mauro Martins
authors.initials: MM
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D004195:Disease Models, Animal; D051379:Mice; D018805:Sepsis / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4