Role of the innate immune system in drug-induced liver injury

TOXI 33

Cynthia Ju, Cynthia.Ju@UCHSC.edu1, Qiang You1, Michael Holt1, Linling Cheng1, and Lance R. Pohl, pohll@nhlbi.nih.gov2. (1) Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, 4200 East Ninth Ave. C238, Denver, CO 80262, (2) Molecular and Cellular Toxicology Section, NIH National Heart Lung and Blood Insitiute, Building 10, Room 8N110, Bethesda, MD 20892-1760
The idiosyncratic nature, severity and poor diagnosis of drug-induced liver injury (DILI) make these reactions a major safety issue during drug development, as well as the most common cause for the withdrawal of drugs from the pharmaceutical market. The key to predicting and preventing DILI is to understand the underlying mechanisms. Our studies using a mouse model of APAP-induced hepatotoxicity suggested a hepato-protective role of hepatic macrophages. Further, we developed a mouse model of halothane-induced liver injury and demonstrated that neutrophils play a crucial role in aggravating tissue damage. Studies by us and others provide evidence that the initiation of hepatocyte injury, caused by a drug or a reactive metabolite of a drug, triggers cells of the innate immune system, and that these cells play important roles in escalating or protecting liver injury.
 

Drug Safety
2:00 PM-5:00 PM, Tuesday, August 21, 2007 BCEC -- 258C, Oral

Division of Chemical Toxicology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007