Cytokine Profile Changes During the Initial Stage of Treatment for Childhood Epstein–Barr Virus-Associated Hemophagocytic Lymphohistiocytosis

Abstract

Hemophagocytic lymphohistiocytosis (HLH) associated with Epstein–Barr virus (EBV) infection ranges from self-limiting to severe/aggressive or fatal. We report the case of a 4-year-old boy with EBV-HLH with persistent fever, severe pancytopenia, hypertriglyceridemia, and hypofibrinogenemia. The levels of plasma cytokines and chemokines were measured using a Bio-Plex system on Days 1, 2, 3, 4, 5, and 8 following hospital admission. The administration of steroid and high-dose intravenous immunoglobulin (1 g/kg) did not alleviate the fever or reduce cytokine production; however, following etoposide (a known antineoplastic agent) administration, the fever decreased immediately, and the patient' s general condition improved. The present study revealed that IL-6, IL-10, IL-8, MCP-1, IFN-γ, and TNF-α were suppressed by etoposide administration. In particular, production of IFN-γ sharply declined from 1,104.1 pg/mL to 101.5 pg/mL, and the IL-6 level also decreased from 229.8 pg/mL to 11.0 pg/mL the day after the initial etoposide administration. Subsequently, there was no recurrence of symptoms with dexamethasone, etoposide, and cyclosporine A treatment. The present case demonstrates that early etoposide administration is critical for successful treatment and indicates that etoposide exhibits a prompt inhibitory effect on cytokine production.