title: Oversecretion of IL-18 in haemophagocytic lymphohistiocytosis: a novel marker of disease activity.
abstract: 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)-gamma 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-gamma (CC 0.711, P = 0.018), and IFN-gamma and sFasL (CC 0.849, P = 0.0049) levels were significantly correlated. On the other hand, correlation between IL-12 and IFN-gamma, IL-18 and sFasL, or IL-18 and IL-12 was not observed. IL-18, IFN-gamma 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.
authors.affiliation: Department of Paediatrics, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takada
authors.forename: S
authors.initials: S
authors.lastname: Ohga
authors.forename: Y
authors.initials: Y
authors.lastname: Mizuno
authors.forename: A
authors.initials: A
authors.lastname: Suminoe
authors.forename: A
authors.initials: A
authors.lastname: Matsuzaki
authors.forename: K
authors.initials: K
authors.lastname: Ihara
authors.forename: N
authors.initials: N
authors.lastname: Kinukawa
authors.forename: K
authors.initials: K
authors.lastname: Ohshima
authors.forename: K
authors.initials: K
authors.lastname: Kohno
authors.forename: M
authors.initials: M
authors.lastname: Kurimoto
authors.forename: T
authors.initials: T
authors.lastname: Hara
mesh_terms: D002450:Cell Communication; D053222:Fas Ligand Protein; D005260:Female; D015616:Histiocytosis, Non-Langerhans-Cell / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D020382:Interleukin-18; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D007371:Interferon-gamma