Interleukin-18 (IL-18) is a proinflammatory cytokine in the IL-1 family that exerts distinct immune effects depending on the local cytokine environment. It is expressed as a 24 kDa precursor by endothelial and epithelial cells, keratinocytes, gamma delta T cells, and phagocytes. The precursor is activated intracellularly by Caspase-1 mediated proteolysis to release the 17 kDa mature cytokine. The precursor can also be released by necrotic cells for extracellular cleavage by multiple proteases. IL-18 activation is induced by infection or tissue damage and contributes to disease pathology in chronic inflammation. IL-18 binds to the widely expressedIL-18 R alpha which recruits IL-18 R beta to form the signaling receptor complex. Its bioactivity is negatively regulated by interactions with IL-18 binding proteins and virally encoded IL-18BP homologs. In the presence of IL-12 or IL-15, IL-18 enhances anti-viral Th1 immune responses by inducing IFN-gamma production and the cytolytic activity of CD8+ T cells and NK cells. In the absence of IL-12 or IL-15, however, IL-18 promotes production of the Th2 cytokines IL-4 and IL-13 by CD4+ T cells and basophils. In the presence of IL-1 beta or IL-23, IL-18 induces the antigen-independent production of IL-17 by gamma delta T cells and CD4+ T cells. IL-18 also promotes myeloid dendritic cell maturation and triggers neutrophil respiratory burst. In cancer, IL-18 exhibits diverse activities including enhancing anti-tumor immunity, inhibiting or promoting angiogenesis, and promoting tumor cell metastasis. Mature human IL-18 shares approximately 63% amino acid sequence identity with mouse and rat IL-18. Alternative splicing in human ovarian cancer generates an isoform that is resistant to Caspase-1 activation. A cell surface form can be expressed on M-CSF induced macrophages and released in response to bacterial endotoxin.
Source
Escherichia coli.
Molecular Weight
Biological Activity
Test in process.
Appearance
Sterile Filtered White lyophilized (freeze-dried) powder.
Formulation
Lyophilized from a 0.2 um filtered solution in PBS, pH 7.0.
Endotoxin
Less than 0.1 EU/ug of rHuIL-18 as determined by LAL method.
Reconstitution
We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Reconstitute in sterile distilled water or aqueous buffer containing 0.1 % BSA to a concentration of 0.1-1.0 mg/mL. Stock solutions should be apportioned into working aliquots and stored at ≤ -20 °C. Further dilutions should be made in appropriate buffered solutions.
Stability and Storage
Use a manual defrost freezer and avoid repeated freeze-thaw cycles.- 12 months from date of receipt, -20 to -70 °C as supplied.- 1 month, 2 to 8 °C under sterile conditions after reconstitution.- 3 months, -20 to -70 °C under sterile conditions after reconstitution.
