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

We investigated the significance of interleukin (IL)-18 levels in the patho physiology of haemophagocytic lymphohistiocytosis (HLH). IL-18 levels were significantly elevated in all nine patients with active HLH compared with t hose of healthy controls. Serial determination of IL-18 levels in three cas es, 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 activit y IL-18 and IFN-gamma (CC 0.711, P=0.018), and IFN-gamma and sFasL (CC 0.84 9, P = 0.0049) levels were significantly correlated. On the other hand, cor relation between IL-12 and IFN-gamma, IL-18 and sFasL, or IL-18 and IL-12 w as 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 syn drome (LAPIS). These results suggest that IL-18 may play important roles in the pathogenesis of HLH, particularly through induction of Th1 cells. IL-1 8 measurement may be useful for the diagnosis and for the detection of smou ldering disease activity.