Retinoic Acid-Induced Regulation of Inflammatory Pathways Is a Potential Sepsis Treatment
Hallie H. Dolin, Justin H. Franco, Xiaohuan Chen, Zhixing K. Pan
Abstract
studies using mouse RAW 264.7 macrophages show that RA decreases tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) and increases mitogen-activated protein kinase phosphatase 1 (MKP-1). RA treatment was also associated with the reduced phosphorylation of key inflammatory signaling proteins. Using a lipopolysaccharide and cecal slurry sepsis model, we found that RA significantly reduced mortality rates in mice, downregulated proinflammatory cytokine production, decreased neutrophil infiltration into lung tissue, and reduced the destructive lung histopathology typically seen in sepsis. We propose that RA may increase the function of native regulatory pathways and serve as a novel treatment for sepsis.