Severe imbalance of IL-18/IL-18BP in patients with secondary hemophagocytic syndrome
Open accessAbstract
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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Patients with cytokine storm due to macrophage activation syndrome have high serum levels of interleukin-18.
“Patients with cytokine storm due to macrophage activation syndrome have high levels of interleukin-18 in serum,44”
From Cytokine storm (2020) · cites this paper as [44]
The ratio of free interleukin-18 to bound interleukin-18-IL18BP complexes in serum is an important indicator of the severity of macrophage activation syndrome.
“The ratio of free interleukin-18 to bound interleukin-18–IL18BP complexes in serum is an important indicator of the severity of the macrophage activation syndrome.44,47”
From Cytokine storm (2020) · cites this paper as [44]
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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
- 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 › Surgery › 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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