title: B-1 cells temper endotoxemic inflammatory responses.
abstract: Sepsis syndrome is caused by inappropriate immune activation due to bacteria and bacterial components released during infection. This syndrome is the leading cause of death in intensive care units. Specialized B-lymphocytes located in the peritoneal and pleural cavities are known as B-1 cells. These cells produce IgM and IL-10, both of which are potent regulators of cell-mediated immunity. It has been suggested that B-1 cells modulate the systemic inflammatory response in sepsis. In this study, we conducted in vitro and in vivo experiments in order to investigate a putative role of B-1 cells in a murine model of LPS-induced sepsis. Macrophages and B-1 cells were studied in monocultures and in co-cultures. The B-1 cells produced the anti-inflammatory cytokine IL-10 in response to LPS. In the B-1 cell-macrophage co-cultures, production of proinflammatory mediators (TNF-α, IL-6 and nitrite) was lower than in the macrophage monocultures, whereas that of IL-10 was higher in the co-cultures. Co-culture of B-1 IL-10(-/-) cells and macrophages did not reduce the production of the proinflammatory mediators (TNF-α, IL-6 and nitrite). After LPS injection, the mortality rate was higher among Balb/Xid mice, which are B-1 cell deficient, than among wild-type mice (65.0% vs. 0.0%). The Balb/Xid mice also presented a proinflammatory profile of TNF-α, IL-6 and nitrite, as well as lower levels of IL-10. In the early phase of LPS stimulation, B-1 cells modulate the macrophage inflammatory response, and the main molecular pathway of that modulation is based on IL-10-mediated intracellular signaling.
authors.affiliation: Clinical Laboratory in Emergency Medicine, University of São Paulo, School of Medicine, São Paulo, Brazil. denisedna@hotmail.com
authors.forename: Denise Frediani
authors.initials: DF
authors.lastname: Barbeiro
authors.forename: Hermes Vieira
authors.initials: HV
authors.lastname: Barbeiro
authors.forename: Joel
authors.initials: J
authors.lastname: Faintuch
authors.forename: Suely K Kubo
authors.initials: SK
authors.lastname: Ariga
authors.forename: Mario
authors.initials: M
authors.lastname: Mariano
authors.forename: Ana Flávia
authors.initials: AF
authors.lastname: Popi
authors.forename: Heraldo Possolo
authors.initials: HP
authors.lastname: de Souza
authors.forename: Irineu Tadeu
authors.initials: IT
authors.lastname: Velasco
authors.forename: Francisco Garcia
authors.initials: FG
authors.lastname: Soriano
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D018920:Coculture Techniques; D019446:Endotoxemia / Q000276:immunology*; D055786:Gene Knockout Techniques; D007249:Inflammation / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009573:Nitrites / Q000276:immunology; D010529:Peritoneal Cavity; D035422:Pleural Cavity / Q000276:immunology; D018805:Sepsis; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10