Role of immune reactions in drug-induced liver injury (DILI).

Although some drugs cause drug-induced liver injury (DILI) through direct damage to hepatocytes or intereference with bile secretion, others cause delayed, often idiosyncratic, DILI with clinical features, such as mild lymphocytic infiltrate, that are reminiscent of allergic reactions involving activation of the adaptive immune system. Even in cases of direct drug-induced hepatotoxicity, infiltration of inflammatory cells into the liver is often observed, suggesting a role for the innate immune system (e.g., neutrophils, macrophages, and so on). Therefore, a variety of hypotheses for the pathogenesis of DILI center around a pathogenic role of drug- (or drug-metabolite-) specific adaptive immune cells, as well as hepatic-injury-induced innate immune responses in the development, progression, and/or resolution of DILI.