0 (Bio-Rad). The levels of interleukin (IL)-1β, IL-10, IL-12, IL-13 and tumor necrosis factor (TNF)-α were elevated before the liver enzyme elevation (Fig. 2). The levels of IL-4, IL-5, IL-6, IL-8, IL-17, monocytic chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β) immediately became elevated after the liver enzyme elevation and then dramatically decreased 2–3 days after peaking (Fig. 2). DRUG-INDUCED LIVER INJURY is classified into two types: the intrinsic type

and the idiosyncratic type.[2, 5, 6] Most cases of DILI are idiosyncratic, accounting for 13% of cases of acute liver failure in the USA.[1] In order to prevent and treat find more idiosyncratic DILI, the pathogenesis of the condition must be understood. However, because DILI is usually diagnosed retrospectively, the detailed mechanisms underlying the development of DILI

remain unclear. Because a subset of idiosyncratic DILI patients present with rashes, fever or eosinophilia, the disease is considered to be associated with the immune response.[2] Therefore, cytokine interactions may play an important role in the pathogenesis of DILI. We first reported the simultaneous evaluation of serial changes in the levels of several cytokines before the initiation of liver injury in humans and found that the elevation of the IL-1β, IL-10, IL-12, IL-13 and TNF-α levels Rucaparib order preceded the liver enzyme elevation. These findings suggest that these cytokines play important roles in the initial stage of DILI. Because alcoholic

liver injury and pneumonia were present as pre-existing diseases in this case, the levels of several Methocarbamol cytokines were not within the normal ranges on the 15th hospital day, although the patient was asymptomatic. Because we did not store any samples before the 15th hospital day in this case, we were not able to ascertain what cytokine was the initiation cytokine in onset of DILI. Sustained high levels of several cytokines in patients with pneumonia or alcoholic liver injury after treatment have been previously reported.[7-10] Therefore, the influence of alcoholic liver injury and pneumonia on the cytokine levels cannot be completely excluded in this case. In fact, the levels of most cytokines in this case were high to normal even within 52 days after the administration of treatment.[11] However, the levels of several cytokines that were high before onset immediately decreased after the administration of antibiotics was discontinued as shown in the profile of IL-1β. Therefore, these cytokines acted as preconditioning cytokines in this case. We hypothesized the following mechanism of liver injury in the present case. Because IL-1β and TNF-α, which are pro-inflammatory cytokines, were at a high level before the elevation of liver enzymes, these cytokines functioned as preconditioning cytokines.