Suppression of Dendritic Cell-Derived IL-12 by Endogenous Glucocorticoids Is Protective in LPS-Induced Sepsis

• Published in: PLoS biology Vol. 13; no. 10; p. e1002269
• Main Authors: Li, Caiyi C, Munitic, Ivana, Mittelstadt, Paul R, Castro, Ehydel, Ashwell, Jonathan D
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.10.2015; Public Library of Science (PLoS)
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Antibodies, Neutralizing - administration & dosage; Antibodies, Neutralizing - therapeutic use; Care and treatment; CD11c Antigen - genetics; CD11c Antigen - metabolism; Cells, Cultured; Corticosteroids; Crosses, Genetic; Cytokines; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - pathology; Dose-Response Relationship, Drug; Experiments; Female; Flow cytometry; Glucocorticoids - agonists; Glucocorticoids - antagonists & inhibitors; Glucocorticoids - blood; Glucocorticoids - metabolism; Health aspects; Immunity, Innate - drug effects; Immunotherapy; Inflammation; Interleukin-12 - antagonists & inhibitors; Interleukin-12 - blood; Interleukin-12 - metabolism; Lipopolysaccharides - toxicity; Male; Medical research; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Mortality; Receptors, Glucocorticoid - agonists; Receptors, Glucocorticoid - antagonists & inhibitors; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - metabolism; Risk factors; Rodents; Sepsis; Septic shock; Shock, Septic - immunology; Shock, Septic - metabolism; Shock, Septic - pathology; Shock, Septic - prevention & control; Signal Transduction - drug effects; Software; Specific Pathogen-Free Organisms; Spleen - drug effects; Spleen - immunology; Spleen - metabolism; Spleen - pathology; Statistical analysis; United States

Sepsis, an exaggerated systemic inflammatory response, remains a major medical challenge. Both hyperinflammation and immunosuppression are implicated as causes of morbidity and mortality. Dendritic cell (DC) loss has been observed in septic patients and in experimental sepsis models, but the role of...