The role of interleukin-6 in the failure of neutrophil migration to focus of infection in sepsis

• Grant number: 11/19135-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2011
• Effective date (End): July 31, 2012
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Fernando de Queiroz Cunha
• Grantee: Ana Elisa Ferreira
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Sepsis develops when the initial host immune response is unable to contain the primary infection, resulting in a generalized inflammation and multiple organ dysfunction due to generalized infection. Our group has shown that the impairment of neutrophil migration to infectious focus is a characteristic observed in sepsis and is directly related to the survival rate. Interleukin (IL) -6 is known to be an important proinflammatory cytokine that is elevated during sepsis, but data in the literature are controversial, since this mediator possesses protective or harmful to their development. The objective of this work is to investigate the role of IL-6 in the failure of neutrophil migration to focus of infection and developing a systemic inflammatory response induced by CLP model (cecal ligation and puncture) in wild-type mice and IL-6 deficient mice for assessing the following parameters: a) survival, b) Migration of neutrophils to the infection, c) Circuit of the infectious process by the bacteria count in the peritoneal cavity and blood d) Serum and peritoneal cavity of cytokines, e) Determination of leukocyte infiltration in tissues, f) Rolling and adhesion of leukocytes g) Expression of the chemotactic receptor CXCR2, h) Expression of the GRK2 protein i) neutrophil chemotaxis induced by MIP-2 in Boyden chamber. (AU)