Description
Biological activity
Background information
IL-18 is a pro-inflammatory cytokine and is a member of the IL-1 cytokine family, which comprises cytokines like IL-1β, IL-33 and IL-36. Like other members of this family, IL-18 is expressed as an inactive 24 kDa precursor covering 193 amino acids7,8.
Similar to other IL-1 family members, the molecular structure of IL-18 contains a β-trefoil arrangement9. Due to the lack of a signal peptide, the IL-18 precursor accumulates in the cytoplasm, where it can be activated by proteolytic processing by Caspase-17,8. Active Caspase-1 also cleaves Gasdermin D to liberate a pore-forming domain, which allows secretion of the mature 17.2 kDa IL-1810.
IL-18 is a pleiotropic cytokine, mainly expressed by macrophages. Its most prominent biological function is its ability to induce IFN-γ expression by CD8+ T cells, Th1 cells as well as NK and CD4+ NKT cells. The presence of IL-12 enhances the IFN-γ expression significantly and a combination of IL-12 and IL-18 can synergize to induce IFN-γ expression from DCs, Møs and B cells10. IL-18 therefore plays a crucial part in the host defense against both bacterial and viral pathogens, as IL-18 induced IFN-γ strongly enhances phagocytosis, NO and ROS production by macrophages and enhances activation of CTLs10. In the absence of IL-12, IL-18 plays a role in Th2 diseases, as it can induce expression of large amounts of IL-4 and IL-13 from basophils and mast cells11.
Apart from its obvious role in host defense, IL-18 has also been implicated in playing a beneficial role in metabolic homeostasis, as it has been demonstrated that IL-18-deficient mice spontaneously developed obesity and insulin resistance10. Moreover, in several human autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Type-1 diabetes, Crohn’s disease and psoriasis, elevated levels of IFN-γ and IL-18 have been observed – implicating an involvement of IL-18 in the disease mechanism.11
The receptor for IL-18 is comprised of two subunits, the inducible IL-18Rα and the constitutively expressed IL-18Rβ. Both subunits contain an intracellular TIR signaling domain, similar to other IL-1 family cytokine receptors and TLRs. Stimulation of naïve T cells with IL-12 results in the upregulation of IL-18Rα, rendering these cells susceptible to IL-18 signaling10.
Applications
MACS GMP Recombinant Human IL-18 can be used for a variety of applications, including:
- Generation of cytokine-induced memory-like natural killer cells (CIML NK). Memory-like NK cells can be generated ex vivo by cultivating human NK cells with a combination of IL-12, IL-15 and IL-18. Such CIML NK cells demonstrated an increased longevity and enhanced anticancer functionality compared to normal effector NK cells1.
- Ex vivo expansion of NK cells. In concert with IL-2, IL-15, IL-12 and IL-21, IL-18 is a key player in the priming, expansion and survival of NK cells2, 3, 4.
- Optimization of ex vivo manufacturing protocols for adoptive cell transfer. Studies in animal models have demonstrated that cultivation of HER2-CAR T cells in the presence of IL-18 can improve anti-tumor functions and increase the amount of TCM cells in the cellular product5.
Technical specifications
MACS GMP Recombinant Human IL-18 is manufactured and released based on the stringent specifications displayed below. Lot-specific results of the respective QC measurements are depicted on each Product Quality Certificate (PQC). Learn more here
- Identity: Confirmed by mass spectrometry and chip electrophoresis. This corresponds to the mature form of IL-18.
- Purity: ≥ 95 % as determined by chip electrophoresis.
- Endotoxin content: < 50 EU/mg, as determined by kinetic Limulus Amoebocyte Lysate (LAL) assay (Pharmacopoeia Europaea (Ph. Eur.)).
- Residual host cell DNA content: < 5 ng/mg, as determined by quantitative PCR specific for E.coli genomic DNA.
- Residual host cell protein content: < 10 µg/mg, as determined by E.coli HCP ELISA.
MACS GMP Recombinant Human IL-18 is expressed as a single chain protein, covering amino acids 37-193 of the amino acid sequence of human interleukin 18 (UniProt Q14116). This sequences corresponds to the mature form of IL-18 after proteolytic cleavage.
Quality statement
MACS GMP Products are manufactured and tested under a quality management system (ISO 13485) and are in compliance with relevant GMP guidelines. They are designed following the recommendations of USP <1043> on ancillary materials.
Disclaimer
MACS GMP Products are for ex vivo cell processing only, and are not intended for human in vivo applications. For regulatory status in the USA, please contact your local representative.
Overview
MACS GMP Recombinant Human Interleukin-18 (IL-18) is a recombinant protein optimized as an ancillary material for ex vivo cell processing. It is not intended for human in vivo applications.
