Eotaxin expression and eosinophil infiltrate in the liver of patients with drug-induced liver disease

Background: Drug-induced liver disease is due to intrinsic or idiosyncratic hepatotoxins. Liver parenchyma is then infiltrated by immunocompetent cells. Eosinophils are primarily tissue leukocytes which are attracted into tissues by various chemoattractants, including chemokines. The aim of this study was to study eosinophils in the livers of patients with drug-induced liver disease. Methods: Immunohistochemical studies with antibodies against eosinophil cationic proteins (major basic protein, eosinophil-derived neurotoxin and eosinophil cationic protein), cytokines (interleukin 5 (IL-5), interleukin 3 (IL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF)) and chemokines (eotaxin and RANTES (Regulated upon Activation Normal T cell Expressed and Secreted)) were performed to assess the in situ activation of the liver-infiltrating eosinophils of 14 patients with drug-induced liver disease and 19 controls. Results: Eosinophils were only observed in patients with drug-induced liver disease. Eosinophils were morphologically normal when hepatitis was due to paracetamol whereas eosinophils had granular changes when hepatitis was due to an idiosyncratic hepatotoxin. Eotaxin was detected in all patients with drug-induced liver disease, whereas RANTES was detected in three of them. IL-5, IL-3 or GM-CSF were not detected. Conclusions: In patients with drug-induced liver disease, the recruitment of eosinophils in the liver may depend on eotaxin expression. Eosinophil changes may vary according to the type of drug.