Hypercytokinemia in Familial Hemophagocytic Lymphohistiocytosis

• Published in: Blood Vol. 78; no. 11; pp. 2918 - 2922
• Main Authors: Henter, Jan-Inge, Elinder, Göran, Söder, Olle, Hansson, Mona, Andersson, Birger, Andersson, Ulf
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01-12-1991; The Americain Society of Hematology
• Subjects: Biological and medical sciences; CD8 Antigens - blood; Child, Preschool; Female; Hematologic and hematopoietic diseases; Histiocytosis, Non-Langerhans-Cell - blood; Histiocytosis, Non-Langerhans-Cell - genetics; Histiocytosis, Non-Langerhans-Cell - pathology; Humans; Infant; Interferon-gamma - blood; Interleukin-6 - blood; Male; Medical sciences; Other diseases. Hematologic involvement in other diseases; Tumor Necrosis Factor-alpha - metabolism; Human; Pathogenesis; Cytokine; Exploration; Hemopathy; Inflammation; Familial histiocytic reticulosis; Child
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V78.11.2918.2918

Familial hemophagocytic lymphohistiocytosis (FHL) is a frequently missed and almost uniformly fatal childhood disorder. It is characterized by fever, hepatosplenomegaly, cytopenia, coagulopathy, and hypertriglyceridemia. The pathogenesis of FHL is not known but the above clinical and laboratory findings are compatible with reported in vitro and in vivo effects of several inflammatory cytokines. We measured circulating interferon-γ (IFN-γ), tumor necrosis factor/cachectin (TNF), and interleukin-6 (IL-6) in nine children with FHL. During active disease, elevated IFN-γ was detected in seven of seven children, TNF in six of six, and IL-6 in two of six children studied. Thus, important inflammatory cytokines are augmented in active FHL and may contribute to the pathogenesis of the disease. Soluble CD8 was also increased in seven of seven children, which suggests a pathophysiologic importance of cytotoxic T lymphocytes. Because FHL appears to be associated with a systemic hypercytokinemia, our results also indicate that studies of FHL may contribute to the understanding of cytokine effects in vivo. Moreover, FHL is a hereditary disorder, suggesting that the hypercytokinemia is caused by a genetic defect in cytokine regulation.