Involvement of interferon‐γ and macrophage colony‐stimulating factor in pathogenesis of haemophagocytic lymphohistiocytosis in adults

Abstract

Summary We investigated the role of monocyte/macrophage‐activating cytokines in pathogenesis of haemophagocytic lymphohistiocytosis (HLH) in 21 adult patients. Sera from patients with active HLH contained extremely high levels of macrophage colony‐stimulating factor (M‐CSF) and of interferon‐γ (IFN‐γ). These levels returned to almost normal during remission. Neither interleukin‐4 nor granulocyte/macrophage colony‐stimulating factor could be detected. Active HLH sera also contained high concentrations of inflammatory monokines, such as interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α). Serum concentrations of soluble CD8 and soluble interleukin‐2 receptor were extremely high during active HLH, and returned to virtually normal levels during remission. Circulating CD2+ T‐cells obtained from patients with active HLH spontaneously secreted M‐CSF and IFN‐γ in vitro, whereas circulating monocytes did not produce detectable levels of both M‐CSF and IFN‐γ, but produced high levels of IL‐6 and TNF‐α. These findings suggest that IFN‐γ and M‐CSF at least partly from T‐cells, such as CD8+ T‐cells, might contribute to activation of monocytes or histiocytes, resulting in the up‐regulated monokine production and haemophago‐cytosis in HLH.