B-1 cells temper endotoxemic inflammatory responses

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• 作者：Denise Frediani Barbeiro^a ; ^{denisedna@hotmail.com} ; Hermes Vieira Barbeiro^a ; Joel Faintuch^b ; Suely K. Kubo Ariga^a ; Mario Mariano^c ; Ana Flá ; via Popi^c ; Heraldo Possolo de Souza^a ; Irineu Tadeu Velasco^a ; Francisco Garcia Soriano^a
• 关键词：Cytokines ; Inflammation ; LPS ; Macrophage ; Sepsis
• 刊名：Immunobiology
• 出版年：2011
• 出版时间：March 2011
• 年：2011
• 卷：216
• 期：3
• 页码：302-308
• 全文大小：635 K

文摘

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.