Oversecretion of IL‐18 in haemophagocytic lymphohistiocytosis: a novel marker of disease activity

• Published in: British journal of haematology Vol. 106; no. 1; pp. 182 - 189
• Main Authors: Takada, Hidetoshi, Ohga, Shouichi, Mizuno, Yumi, Suminoe, Aiko, Matsuzaki, Akinobu, Ihara, Kenji, Kinukawa, Naoko, Ohshima, Koichi, Kohno, Keizo, Kurimoto, Masashi, Hara, Toshiro
• Format: Journal Article
• Language: English
• Published: Oxford, U.K. and Cambridge, USA Blackwell Science Ltd 01.07.1999; Blackwell; Blackwell Publishing Ltd
• Subjects: Biological and medical sciences; Cell Communication; Fas Ligand Protein; Female; haemophagocytic lymphohistiocytosis; Hematologic and hematopoietic diseases; Hematology; Histiocytosis, Non-Langerhans-Cell - diagnosis; Histiocytosis, Non-Langerhans-Cell - metabolism; Humans; Interferon-gamma - metabolism; interferon‐gamma; Interleukin-18 - metabolism; interleukin‐18; Male; Medical sciences; Membrane Glycoproteins - metabolism; Other diseases. Hematologic involvement in other diseases; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; soluble Fas ligand; T-Lymphocytes - physiology; Th1 cells; Human; Hemophagocytic syndrome; Hemophagocytic lymphohistiocytosis; Pathogenesis; Cytokine; Evolutivity; Biological marker; Hemopathy; Interleukin 18
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.1999.01504.x

We investigated the significance of interleukin (IL)‐18 levels in the pathophysiology of haemophagocytic lymphohistiocytosis (HLH). IL‐18 levels were significantly elevated in all nine patients with active HLH compared with those of healthy controls. Serial determination of IL‐18 levels in three cases, showed a gradual decrease compared with those of IL‐12, interferon (IFN)‐γ or soluble Fas ligand (sFasL) in the course of clinical improvement, and seemed to be elevated until complete disappearance of disease activity. IL‐18 and IFN‐γ (CC 0.711, P = 0.018), and IFN‐γ and sFasL (CC 0.849, P = 0.0049) levels were significantly correlated. On the other hand, correlation between IL‐12 and IFN‐γ, IL‐18 and sFasL, or IL‐18 and IL‐12 was not observed. IL‐18, IFN‐γ and sFasL levels significantly correlated with disease activity such as fever and alanine transaminase (ALT) levels. IL‐18 mRNA expression was enhanced in spleen, but not in peripheral blood mononuclear cells (MNC), bone marrow MNC, liver from patients of active HLH, or the tumour from a patient with lymphoma‐associated haemophagocytic syndrome (LAHS). These results suggest that IL‐18 may play important roles in the pathogenesis of HLH, particularly through induction of Th1 cells. IL‐18 measurement may be useful for the diagnosis and for the detection of smouldering disease activity.