Increased serum levels of interferon-γ-inducible protein 10 and monokine induced by gamma interferon in patients with haemophagocytic lymphohistiocytosis

Abstract

We measured serum interferon‐gamma‐inducible protein 10 (IP‐10) and monokine induced by gamma interferon (MIG) levels to investigate the role of these molecules in the pathophysiology of haemophagocytic lymphohistiocytosis (HLH). Serum IP‐10 and MIG levels were significantly increased in patients with active HLH compared with those of healthy controls. Serum MIG levels decreased gradually during the course of disease in a patient who recovered without therapy. On the other hand, rapid reduction of MIG and IP‐10 levels was observed after chemotherapy in a patient with severe HLH. IP‐10 and MIG mRNA expression was enhanced in liver and spleen, and IP‐10 mRNA expression was enhanced in bone marrow in the patients, suggesting activated macrophages that infiltrated in these organs as one of the main producers of these cytokines. Serum IP‐10 and MIG levels showed a significant correlation with serum IFN‐γ levels. In addition, these chemokines had a significant correlation with fever and serum LDH levels, which are clinical indicators of disease activity of HLH. These results suggest that IP‐10 and MIG which are produced by activated macrophages by the stimulation of IFN‐γ, play an important role in the pathophysiology of HLH, by recruitment of activated Th1 cells into the tissues or organs.