Cited by 290Autoimmune and Inflammatory Disorders ResearchImmunodeficiency and Autoimmune DisordersKawasaki Disease and Coronary Complications

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Severe imbalance of IL-18/IL-18BP in patients with secondary hemophagocytic syndrome

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Mazodier, K.·2005·Blood

DOI 10.1182/blood-2005-05-1980PMC PMC1895045

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Abstract

Hemophagocytic syndrome (HPS) is characterized by an uncontrolled and poorly understood activation of T-helper 1 (Th-1) lymphocytes and macrophages. We studied 20 patients with HPS secondary to infections, autoimmune disease, lymphoma, or cancer and observed that the concentrations of serum interleukin 18 (IL-18), a strong inducer of Th-1 responses, interferon gamma (IFN-gamma) production, and stimulation of macrophages and natural killer (NK) cells were highly increased in HPS but not in control patients. In contrast, concentrations of its natural inhibitor, the IL-18 binding protein (IL-18BP), were only moderately elevated, resulting in a high level of biologically active free IL-18 in HPS (4.6-fold increase compared with controls; P < .001). Free IL-18 but not IL-12 concentrations significantly correlated with clinical status and the biologic markers of HPS such as anemia (P < .001), hypertriglyceridemia, and hyperferritinemia (P < .01) and also with markers of Th-1 lymphocyte or macrophage activation, such as elevated concentrations of IFN-gamma and soluble IL-2 and tumor necrosis factor alpha (TNF-alpha) receptor concentrations. Despite high IL-18 elevation, in vitro NK-cell cytotoxicity was severely impaired in HPS patients, in part due to NK-cell lymphopenia that was observed in a majority of patients but also secondary to an intrinsic NK-cell functional deficiency. We concluded that a severe IL-18/IL-18BP imbalance results in Th-1 lymphocyte and macrophage activation, which escapes control by NK-cell cytotoxicity and may allow for secondary HPS in patients with underlying diseases.

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Authors: Mazodier, K.
Affiliations: Inserm (FR)
Corresponding author: Mazodier, K.
Venue: Blood
Publisher: American Society of Hematology
Published: 2005-11-15
Volume: 106
Issue: 10
Pages: 3483-3489
ISSN: 0006-4971 (ISSN-L)
1528-0020
DOI: 10.1182/blood-2005-05-1980
PMC: PMC1895045
OpenAlex: W2157675757
Cited by: 290
References: 47
Citations by year: 2026: 7 · 2025: 6 · 2024: 19 · 2023: 16 · 2022: 16 · 2021: 17 · 2020: 13 · 2019: 19 · 2018: 19 · 2017: 18 · 2016: 14 · 2015: 13 · 2014: 17 · 2013: 13 · 2012: 12
FWCI: 5.34
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Blood (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Heart, Lung, and Blood Institute (HL68743, P01HL068743)
National Institute of Allergy and Infectious Diseases (AI‑15614)
Topics: Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Kawasaki Disease and Coronary Complications
Keywords: hemophagocytic lymphohistiocytosis, secondary hemophagocytic lymphohistiocytosis, IL-18, IL-18BP, macrophage activation, interferon-gamma, NK cell cytotoxicity, hyperferritinemia, hypertriglyceridemia, anemia, soluble interleukin-2 receptor, TNF-alpha receptor, cytokine imbalance
MeSH terms: Adolescent, Adult, Aged, Aged, 80 and over, Autoimmune Diseases, Female, Glycoproteins, Humans, Leukocytes, Lymphocyte Activation, Lymphopenia, Macrophage Activation, Male, Middle Aged, Neoplasms, Prospective Studies, Biomarkers, Cytokines, Interleukin-18, Intercellular Signaling Peptides and Proteins, Lymphohistiocytosis, Hemophagocytic

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Severe imbalance of IL-18/IL-18BP in patients with secondary hemophagocytic syndrome

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