Cytokine and autoantibody patterns in acute liver failure

Abstract

The mechanisms of idiosyncratic drug-induced liver injury (IDILI) are still a matter of dispute. Some of the characteristics of reactions that have been classed as metabolic idiosyncrasy could also be those of an immune-mediated reaction with an autoimmune component. Many auto-immune reactions appear to be mediated by TH17 cells, which are in part characterized by the production of interleukin (IL)-17. To test the involvement of TH17 cells in IDILI, we quantified a number of cytokines, chemokines, and autoantibodies in the serum of 39 patients with acute liver failure (ALF) due to IDILI and compared the values with those from 21 patients with acetaminophen-induced ALF and 10 patients with viral hepatitis-induced ALF. The IL-17 levels were elevated in 60% of patients with IDILI, but also in a similar number of patients with acetaminophen-induced ALF and occasionally in patients with viral hepatitis. Levels of other cytokines, such as IL-21, that are also produced by TH17 cells were higher in patients with IDILI, but again, there was overlap with acetaminophen DILI. Autoantibodies were more frequent in patients in the IDILI group but were absent in most patients. These data provide a picture of the cytokine/chemokine profile in patients with various types of ALF. The pattern varies from patient to patient and not specifically by etiology. This suggests that different underlying disease mechanisms may be at play in different individuals, even among those demonstrating injury from the same drug. Since cytokines may originate from more than one type of cell, interpretation of results of cytokine assays remains difficult in complex disease settings.