GO:0070673 response to interleukin-18: Signaling Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0070673 response to interleukin-18 describes any cellular or organismal change triggered by an interleukin-18 (IL-18) stimulus, including movement, secretion, enzyme production, and gene expression [1, 6].
• IL-18 is a member of the IL-1 cytokine family and is best known for inducing interferon-gamma (IFN-gamma) production in T cells and natural killer (NK) cells [6, 8].
• The response to IL-18 is tightly controlled by the inflammasome, which activates caspase-1 to cleave pro-IL-18 into its mature, secreted form [3, 8].
• Dysregulated IL-18 signaling is implicated in inflammatory diseases, autoinflammatory syndromes, atherosclerosis, and cancer immune escape [1, 2, 3, 5].
• Alternative splicing and caspase-3 cleavage can generate distinct IL-18 isoforms with different biological activities, adding layers of regulation to the response [2, 7].
• CRISPR-based knockout, knock-in, and overexpression models are essential tools for dissecting the causal roles of genes in the IL-18 response pathway [2, 4, 7].
Description
The Gene Ontology term GO:0070673, response to interleukin-18, defines the collection of cellular and organismal processes that are initiated when a cell encounters interleukin-18 (IL-18) [1, 6]. IL-18 is a pleiotropic pro-inflammatory cytokine belonging to the IL-1 family, and its activity spans immune cell activation, cytokine production, and modulation of cell survival and death [6, 8]. Researchers study this term to understand how a single cytokine can orchestrate diverse outcomes, from protective anti-tumor immunity to pathological inflammation [1, 7]. The response to IL-18 is not a single linear pathway; it involves receptor binding, intracellular signaling cascades, transcriptional reprogramming, and post-transcriptional regulation that together shape the cell's fate [1, 8]. Because IL-18 is implicated in a wide range of human diseases, including autoinflammatory disorders, atherosclerosis, and cancer, defining the molecular players in this response is critical for identifying therapeutic targets [1, 2, 3, 5]. This article provides a research-grade overview of GO:0070673, integrating authoritative QuickGO annotation with verified PubMed literature to support experimental design and hypothesis generation [1, 2, 3, 4, 5, 6, 7, 8].
response to interleukin-18 At A Glance
| GO ID | GO:0070673 |
|---|---|
| GO term | response to interleukin-18 |
| Ontology | biological_process |
| Synonym | response to IL-18 |
| Definition | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interleukin-18 stimulus. |
| Major function | Mediates cellular responses to the pro-inflammatory cytokine IL-18, including immune cell activation, cytokine production, and modulation of cell survival [1, 6, 8]. |
| Key upstream regulator | Inflammasome-mediated caspase-1 activation cleaves pro-IL-18 to its mature form [3, 8]. |
| Primary responders | T cells, NK cells, macrophages, and other immune and non-immune cells [6, 8]. |
| Associated diseases | Autoinflammatory syndromes, atherosclerosis, cancer, and inflammatory diseases [1, 2, 3, 5]. |
What Is GO:0070673?
In our own words, GO:0070673 response to interleukin-18 encompasses any process that results in a change in the state or activity of a cell or an organism as a result of an interleukin-18 stimulus. This includes changes in movement, secretion, enzyme production, gene expression, and other cellular activities. The term captures the full spectrum of downstream effects that occur when IL-18 binds to its receptor and triggers intracellular signaling, rather than describing a single molecular event [1, 6, 8].
Why Is response to interleukin-18 Important in Cell Biology?
Understanding GO:0070673 is essential because IL-18 sits at the crossroads of innate and adaptive immunity, and its dysregulation contributes to a broad spectrum of human pathologies [1, 6]. The response to IL-18 can be protective, as seen in its ability to mobilize NK cells against tumors, or detrimental, as in chronic inflammatory diseases where excessive IL-18 signaling drives tissue damage [1, 7]. By dissecting the molecular components of this response, researchers can identify biomarkers and therapeutic targets for conditions ranging from rare autoinflammatory syndromes to common diseases like atherosclerosis and cancer [1, 2, 3, 5].
• IL-18 is a key mediator of inflammation and immune surveillance, making its response pathway a central node in immunology research [1, 6].
• Dysregulated IL-18 signaling is directly linked to autoinflammatory diseases, including those with distinct interferon signatures.
• The NLRP3 inflammasome and IL-1 pathway, which activate IL-18, are major drivers of atherosclerosis.
• IL-18 can promote tumor immune escape through mechanisms such as exon skipping and altered splicing.
• Short IL-18 isoforms generated by caspase-3 cleavage can mobilize NK cells to suppress tumor growth, revealing context-dependent functions.
• Hyper-virulent pathogens can modulate IL-18 secretion by monocytic cells, affecting host defense.
• IL-18 is a potential biomarker and therapeutic target in inflammatory diseases, with clinical roles being actively defined.
• CRISPR screening and knockout models enable causal interrogation of genes within the IL-18 response network [2, 4, 7].
• Understanding IL-18 biology informs vaccine adjuvant design and cancer immunotherapy strategies [7, 8].
• The response to IL-18 intersects with other cytokine pathways, offering opportunities for combination therapies [1, 3].
What Happens During response to interleukin-18?
IL-18 Production and Maturation
In simple terms: Before a cell can respond to IL-18, the cytokine must be made and cut into its active form.
IL-18 is synthesized as an inactive precursor, pro-IL-18, which lacks a signal peptide and is retained in the cytoplasm [6, 8]. In response to danger signals, the NLRP3 inflammasome assembles and activates caspase-1, which cleaves pro-IL-18 into its mature, biologically active form [3, 8]. This maturation step is a critical control point, as only mature IL-18 can be secreted and initiate signaling in target cells [3, 8]. Alternative cleavage by caspase-3 can generate a short IL-18 isoform with distinct functions, such as mobilizing NK cells. Additionally, alternative splicing of IL-18 pre-mRNA, regulated by factors like PTBP3, can produce variants that promote immune escape in cancer.
IL-18 Secretion and Receptor Binding
In simple terms: Once active, IL-18 leaves the cell and docks onto its receptor on target cells.
Mature IL-18 is secreted through a non-classical pathway, as it lacks a signal peptide [6, 8]. Upon release, IL-18 binds to the IL-18 receptor complex, composed of IL-18R1 and IL-18RAP subunits, on the surface of target cells [1, 6]. This binding triggers conformational changes that activate intracellular signaling. The availability of IL-18 is further regulated by its natural antagonist, IL-18 binding protein (IL-18BP), which sequesters IL-18 and prevents receptor engagement [1, 6]. Pathogens can also modulate IL-18 secretion; for example, hyper-virulent Streptococcus pyogenes reduces IL-18 secretion by human monocytic cells.
Intracellular Signaling Cascades
In simple terms: After IL-18 binds its receptor, a chain of molecular signals is activated inside the cell.
IL-18 receptor engagement recruits the adaptor protein MyD88, which activates IRAK kinases and TRAF6, leading to NF-kB and MAPK pathway activation [1, 6]. These signaling events drive the transcription of numerous genes, including IFN-gamma, pro-inflammatory cytokines, and chemokines [1, 6]. In T cells and NK cells, IL-18 signaling synergizes with IL-12 to induce robust IFN-gamma production, a hallmark of the IL-18 response [6, 8]. The signaling cascade also involves PI3K/Akt and JAK/STAT pathways, depending on cell type. This complex network ensures that the response to IL-18 is tailored to the cellular context and the presence of co-stimuli [1, 8].
Transcriptional and Post-Transcriptional Reprogramming
In simple terms: The cell changes which genes are turned on or off, and how their RNA messages are processed.
Activated transcription factors such as NF-kB and AP-1 drive the expression of genes involved in inflammation, immune cell recruitment, and cell survival [1, 6]. Post-transcriptional regulation, including alternative splicing, modulates the IL-18 response. For instance, PTBP3 mediates IL-18 exon skipping to promote immune escape in gallbladder cancer. MicroRNAs and RNA-binding proteins can also influence the stability and translation of IL-18-responsive transcripts. These layers of regulation fine-tune the intensity and duration of the response [1, 2].
Cellular Outcomes and Effector Functions
In simple terms: The response to IL-18 leads to specific actions, such as killing infected cells or producing more cytokines.
The ultimate outcomes of IL-18 signaling include enhanced cytotoxicity of NK cells and CD8+ T cells, increased IFN-gamma secretion, and promotion of Th1 responses [6, 8]. In macrophages, IL-18 can induce the production of other pro-inflammatory mediators, amplifying the immune response. Conversely, IL-18 can also promote cell death or survival depending on the context [1, 8]. In cancer, short IL-18 generated by caspase-3 cleavage mobilizes NK cells to suppress tumor growth, highlighting a protective role. However, tumor cells can exploit IL-18 splicing to evade immune detection. These diverse outcomes underscore the pleiotropic nature of the IL-18 response [1, 7].
Key Genes Involved in GO:0070673 response to interleukin-18
The following genes and proteins are central to the response to interleukin-18, as supported by published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| IL18 | Encodes the pro-inflammatory cytokine interleukin-18 | Central ligand; knockout and overexpression models reveal its role in inflammation and cancer [1, 6, 8] |
| IL18R1 | IL-18 receptor subunit 1; binds IL-18 | Mediates initial recognition; essential for signaling [1, 6] |
| IL18RAP | IL-18 receptor accessory protein; required for signaling | Knockout abolishes IL-18 responsiveness [1, 6] |
| MYD88 | Adaptor protein downstream of IL-18 receptor | Key signaling node; knockout blocks NF-kB activation [1, 6] |
| CASP1 | Caspase-1; cleaves pro-IL-18 to mature IL-18 | Inflammasome effector; knockout reduces IL-18 secretion [3, 8] |
| NLRP3 | Inflammasome sensor; activates caspase-1 | Central to IL-18 maturation; linked to atherosclerosis |
| IL18BP | IL-18 binding protein; negative regulator | Sequesters IL-18; overexpression reduces signaling [1, 6] |
| IFNG | Interferon-gamma; key effector cytokine induced by IL-18 | Readout of IL-18 response; knockout impairs Th1 immunity [6, 8] |
| PTBP3 | RNA-binding protein; regulates IL-18 exon skipping | Promotes immune escape in gallbladder cancer |
| CASP3 | Caspase-3; generates short IL-18 isoform | Alternative cleavage; mobilizes NK cells |
| NKG2D | Activating receptor on NK cells | Involved in NK cell-mediated tumor suppression downstream of IL-18 |
| GZMB | Granzyme B; effector molecule in NK cells | Mediates cytotoxicity; regulated by IL-18 signaling |
| PRF1 | Perforin; pore-forming protein in cytotoxic cells | Essential for NK cell killing; linked to IL-18 response |
| TNF | Tumor necrosis factor; pro-inflammatory cytokine | Induced by IL-18 in macrophages |
| IL6 | Interleukin-6; pro-inflammatory cytokine | Upregulated in response to IL-18 |
| CXCL10 | Chemokine; recruits immune cells | Induced by IL-18 in various cell types |
| STAT1 | Signal transducer and activator of transcription 1 | Mediates IFN-gamma signaling downstream of IL-18 |
| NFKB1 | NF-kB subunit; transcription factor | Drives expression of IL-18-responsive genes [1, 6] |
How Is response to interleukin-18 Regulated?
The response to interleukin-18 is regulated at multiple levels. At the extracellular level, IL-18 binding protein (IL-18BP) acts as a decoy receptor, neutralizing IL-18 and preventing receptor engagement [1, 6]. The inflammasome, particularly NLRP3, controls the maturation of pro-IL-18 via caspase-1 activation, and its activity is modulated by danger signals, ion fluxes, and autophagy [3, 8]. Intracellularly, signaling is negatively regulated by SOCS proteins, which dampen cytokine receptor signaling, and by phosphatases that inactivate kinases in the pathway. Post-transcriptional regulation, including alternative splicing mediated by PTBP3, can alter the IL-18 transcript and its protein products. Additionally, caspase-3 cleavage generates a short IL-18 isoform with distinct functions, adding another layer of regulation. These mechanisms ensure that the IL-18 response is tightly controlled to avoid excessive inflammation [1, 3, 8].
response to interleukin-18 and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| IL18 | Autoinflammatory syndromes, atherosclerosis | IL18 knockout mice; ApoE-/- background [1, 3] |
| NLRP3 | Cryopyrin-associated periodic syndromes, atherosclerosis | NLRP3 knock-in mice; CRISPR point mutation [3, 5] |
| PTBP3 | Gallbladder cancer immune escape | PTBP3 knockout cancer cell lines; xenograft models |
| CASP3 | Cancer immune surveillance | Caspase-3 knockout mice; IL-18 isoform knock-in |
| IL18BP | Inflammatory diseases | IL18BP overexpression models; knockout mice [1, 6] |
IL-18 in Autoinflammatory Diseases
Dysregulated IL-18 signaling is a hallmark of several autoinflammatory diseases, including NLRP3-associated syndromes and other conditions with distinct interferon signatures [1, 5]. In these disorders, excessive inflammasome activation leads to elevated mature IL-18, which drives systemic inflammation and tissue damage [1, 3]. Patients often present with recurrent fever, skin rashes, and elevated acute-phase reactants. Targeting IL-18 or its receptor is a promising therapeutic strategy, and clinical trials are ongoing. Understanding the genetic and molecular basis of these diseases requires functional studies using patient-derived cells and CRISPR models.
IL-18 in Atherosclerosis
The NLRP3 inflammasome and IL-1 pathway, which includes IL-18, play a critical role in atherosclerosis. IL-18 promotes plaque instability by inducing IFN-gamma production and enhancing immune cell infiltration into the arterial wall. Elevated IL-18 levels are associated with cardiovascular events, making it a potential biomarker and therapeutic target. Experimental models, such as ApoE-deficient mice, have been instrumental in elucidating the role of IL-18 in plaque progression. CRISPR knockout of IL-18 or its receptor in these models can help establish causality.
IL-18 in Cancer
IL-18 has dual roles in cancer. It can enhance anti-tumor immunity by activating NK cells and T cells, but tumors can also exploit IL-18 signaling to promote immune escape [2, 7]. For example, PTBP3-mediated IL-18 exon skipping in gallbladder cancer leads to a variant that suppresses immune responses. Conversely, short IL-18 generated by caspase-3 cleavage mobilizes NK cells to suppress tumor growth. These context-dependent effects highlight the need for precise models to study IL-18 isoforms and their downstream pathways [2, 7]. CRISPR-based knockout and knock-in of specific IL-18 variants can dissect their contributions to tumor immunity [2, 7].
IL-18 in Infectious Diseases
IL-18 is critical for host defense against intracellular pathogens by promoting IFN-gamma production [6, 8]. However, some pathogens have evolved mechanisms to subvert IL-18 responses. For instance, hyper-virulent Streptococcus pyogenes reduces IL-18 secretion by human monocytic cells, potentially aiding immune evasion. Understanding how pathogens modulate IL-18 signaling can inform vaccine development and antimicrobial strategies [4, 6]. Experimental models using knockout mice or human cell lines can reveal pathogen-specific mechanisms.
From response to interleukin-18-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does IL-18 drive tumor immune escape? | IL18 knockout cancer cells in syngeneic mouse models [2, 7] |
| What is the role of NLRP3 in IL-18 maturation? | NLRP3 knockout macrophages; CRISPR point mutation |
| How does PTBP3 regulate IL-18 splicing? | PTBP3 knockout or knockdown in cancer cell lines |
| Can short IL-18 enhance NK cell cytotoxicity? | Knock-in of caspase-3 cleavage site; overexpression of short IL-18 |
| Does IL-18BP neutralize IL-18 in vivo? | IL18BP transgenic mice; overexpression in disease models |
| What is the impact of IL-18R1 mutations on signaling? | IL18R1 point mutation knock-in cell lines [1, 6] |
How to Study the response to interleukin-18 Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Global gene expression changes | Identify IL-18-inducible genes and splicing events [1, 2] |
| Proteomics | Protein abundance and modifications | Map signaling pathways and secreted factors [1, 4] |
| ELISA/Luminex | Cytokine concentrations | Quantify IL-18, IFN-gamma, and other cytokines [4, 6] |
| CRISPR knockout screening | Gene essentiality for IL-18 response | Discover novel regulators of IL-18 signaling [2, 3] |
| Flow cytometry | Cell surface markers and intracellular cytokines | Assess immune cell activation and IFN-gamma production [6, 7] |
| Confocal microscopy | Subcellular localization and dynamics | Visualize NF-kB translocation and inflammasome assembly |
| Western blot | Protein expression and phosphorylation | Validate signaling activation (e.g., NF-kB, STAT1) [1, 6] |
| Reporter assays | Transcriptional activity of IL-18-responsive promoters | Screen for modulators of IL-18 signaling |
Transcriptomic Analysis
RNA sequencing (RNA-seq) is widely used to profile gene expression changes following IL-18 stimulation, revealing the transcriptional landscape of the response [1, 2]. This method can identify novel IL-18-inducible genes and pathways, as well as alternative splicing events regulated by factors like PTBP3. Single-cell RNA-seq further resolves cell-type-specific responses in heterogeneous populations. CRISPR knockout of candidate genes followed by RNA-seq can establish causal links.
Proteomic and Cytokine Profiling
Mass spectrometry-based proteomics and multiplex cytokine assays (e.g., Luminex, ELISA) quantify secreted proteins and intracellular signaling intermediates in response to IL-18 [1, 4]. These methods are essential for measuring mature IL-18, IFN-gamma, and other effector cytokines [4, 6]. Phosphoproteomics can map signaling cascades activated downstream of the IL-18 receptor. Such approaches have been used to show reduced IL-18 secretion in response to hyper-virulent S. pyogenes.
Functional Genomics and CRISPR Screening
Genome-wide CRISPR knockout screens enable unbiased discovery of genes required for the IL-18 response, such as those involved in inflammasome activation or receptor signaling [2, 3]. Pooled screens coupled with selection for IL-18-induced phenotypes (e.g., IFN-gamma production or cell death) can identify novel regulators. Targeted knock-in of point mutations can dissect specific domains of IL-18 pathway components [1, 7]. These functional genomics tools are powerful for validating hits from transcriptomic studies.
Imaging and Flow Cytometry
Flow cytometry is used to measure surface expression of IL-18 receptors, intracellular cytokine production, and immune cell activation states after IL-18 stimulation [6, 7]. Imaging techniques, such as confocal microscopy, can visualize NF-kB translocation or inflammasome assembly in real time. These methods provide spatial and temporal resolution of the IL-18 response [3, 6]. They are particularly useful for studying NK cell-mediated cytotoxicity induced by short IL-18.
How CRISPR Can Be Used to Study GO:0070673 response to interleukin-18
Knockout
CRISPR knockout of genes such as IL18, IL18R1, NLRP3, or CASP1 in cell lines or primary cells abolishes specific nodes in the IL-18 response, enabling causal inference [2, 3, 4]. For example, NLRP3 knockout macrophages fail to cleave pro-IL-18, demonstrating the inflammasome's role. Knockout of PTBP3 in cancer cells reverses IL-18 exon skipping and restores immune recognition. These models are essential for validating drug targets and understanding disease mechanisms [2, 3].
Point Mutation
CRISPR point mutation introduces specific amino acid changes to dissect protein function. For instance, mutating the caspase-1 cleavage site in pro-IL-18 prevents maturation, while mutating the caspase-3 site blocks short IL-18 generation. Point mutations in IL18R1 can identify residues critical for ligand binding or signaling. Such precision models are invaluable for structure-function studies and for mimicking human disease variants [1, 7].
Knock-in
Knock-in of tagged IL-18 (e.g., FLAG or GFP) allows tracking of protein localization and secretion. Knock-in of disease-associated mutations, such as those found in autoinflammatory syndromes, creates isogenic models to study pathogenesis. Knock-in of short IL-18 isoform can test its specific role in NK cell activation. These models provide physiological expression levels and context [1, 5, 7].
Overexpression
Overexpression of IL-18 or its receptor subunits using CRISPR activation or lentiviral vectors amplifies the response, useful for gain-of-function studies [1, 6]. Overexpression of IL-18BP can suppress IL-18 signaling and serve as a negative control. In cancer models, overexpression of IL-18 variants can reveal their impact on tumor growth and immune evasion [2, 7]. These approaches complement knockout studies to establish sufficiency [1, 2].
How EDITGENE Supports response to interleukin-18 Research
Researchers studying response to interleukin-18-related genes often need to determine whether a candidate gene is causally involved in the pathway or merely correlated with its activation. EDITGENE provides a comprehensive suite of CRISPR-based services to enable such causal studies, from generating knockout cell lines to engineering precise point mutations and knock-in reporters. By leveraging our expertise in gene editing and functional genomics, we help you accelerate discoveries in IL-18 biology and its associated diseases.
Contact EDITGENE today to design your custom CRISPR model for response to interleukin-18 research.
Frequently Asked Questions About response to interleukin-18
What is GO:0070673 response to interleukin-18?
GO:0070673 is a Gene Ontology biological process term that describes any change in a cell or organism resulting from an interleukin-18 stimulus, including changes in movement, secretion, enzyme production, and gene expression [1, 6].
What genes are involved in the response to interleukin-18?
Key genes include IL18, IL18R1, IL18RAP, MYD88, CASP1, NLRP3, IL18BP, IFNG, and PTBP3, among others [1, 2, 3, 6, 8].
How does IL-18 signal inside the cell?
IL-18 binds to its receptor, recruiting MyD88 and activating NF-kB and MAPK pathways, which drive gene expression and effector functions [1, 6].
What diseases are associated with IL-18 dysregulation?
IL-18 dysregulation is linked to autoinflammatory syndromes, atherosclerosis, cancer, and severe infections [1, 2, 3, 4, 5].
What is the role of the inflammasome in IL-18 response?
The NLRP3 inflammasome activates caspase-1, which cleaves pro-IL-18 into its mature, secreted form, a prerequisite for receptor binding and signaling [3, 8].
How can CRISPR be used to study IL-18 signaling?
CRISPR knockout, knock-in, and overexpression models allow researchers to test the causal role of specific genes in the IL-18 response pathway [2, 4, 7].
What is short IL-18 and how is it generated?
Short IL-18 is an isoform generated by caspase-3 cleavage of pro-IL-18; it can mobilize NK cells to suppress tumor growth.
How does PTBP3 affect IL-18 in cancer?
PTBP3 mediates IL-18 exon skipping, producing a variant that promotes immune escape in gallbladder cancer.
What methods are used to study the response to IL-18?
Common methods include RNA-seq, proteomics, ELISA, flow cytometry, and CRISPR screens [1, 2, 4, 6, 7].
Why is IL-18 important in inflammatory diseases?
IL-18 is a potent pro-inflammatory cytokine, and its excessive or dysregulated activity drives tissue damage in autoinflammatory and chronic inflammatory diseases [1, 5].
Conclusion
GO:0070673 response to interleukin-18 captures a complex and clinically relevant biological process that bridges innate and adaptive immunity. From inflammasome-mediated maturation to receptor signaling and downstream effector functions, the IL-18 response is orchestrated by a network of genes and regulatory mechanisms that are active areas of research [1, 2, 3, 6, 7, 8]. Dysregulation of this pathway contributes to autoinflammatory diseases, atherosclerosis, and cancer, making it a prime target for therapeutic intervention [1, 2, 3, 5]. Advances in CRISPR-based models and functional genomics are accelerating our understanding of IL-18 biology and enabling the development of precision therapies [2, 4, 7].
References
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- 3. Grebe A et al.. 2018. NLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis.. Circ Res 122(12):1722-1740 PMID: 29880500
- 4. Tölken LA et al.. 2024. Reduced interleukin-18 secretion by human monocytic cells in response to infections with hyper-virulent Streptococcus pyogenes.. J Biomed Sci 31(1):26 PMID: 38408992
- 5. de Jesus AA et al.. 2020. Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases.. J Clin Invest 130(4):1669-1682 PMID: 31874111
- 6. Gracie JA et al.. 2003. Interleukin-18.. J Leukoc Biol 73(2):213-24 PMID: 12554798
- 7. Shen J et al.. 2025. Short IL-18 generated by caspase-3 cleavage mobilizes NK cells to suppress tumor growth.. Nat Immunol 26(3):416-428 PMID: 39891018
- 8. Yasuda K et al.. 2019. Interleukin-18 in Health and Disease.. Int J Mol Sci 20(3) PMID: 30717382
