title: Involvement of interferon-gamma and macrophage colony-stimulating factor in pathogenesis of haemophagocytic lymphohistiocytosis in adults.
abstract: 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-gamma (IFN-gamma). 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-alpha (TNF-alpha). 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-gamma in vitro, whereas circulating monocytes did not produce detectable levels of both M-CSF and IFN-gamma, but produced high levels of IL-6 and TNF-alpha. These findings suggest that IFN-gamma 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 haemophagocytosis in HLH.
authors.affiliation: Department of Haematology, Harasanshin General Hospital, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Akashi
authors.forename: S
authors.initials: S
authors.lastname: Hayashi
authors.forename: H
authors.initials: H
authors.lastname: Gondo
authors.forename: S
authors.initials: S
authors.lastname: Mizuno
authors.forename: M
authors.initials: M
authors.lastname: Harada
authors.forename: K
authors.initials: K
authors.lastname: Tamura
authors.forename: K
authors.initials: K
authors.lastname: Yamasaki
authors.forename: T
authors.initials: T
authors.lastname: Shibuya
authors.forename: N
authors.initials: N
authors.lastname: Uike
authors.forename: T
authors.initials: T
authors.lastname: Okamura
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016827:CD8 Antigens / Q000097:blood; D002478:Cells, Cultured; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D015616:Histiocytosis, Non-Langerhans-Cell / Q000209:etiology* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D016131:Lymphocyte Subsets / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D016827:CD8 Antigens; D015850:Interleukin-6; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor