Interleukin-18 (IL-18) is a multifunctional cytokine that augments interferon-γ production and acts as an important immunomediator in the development of several types of cancer.
Since regulation of IL-18 activity likely contributes to the pathogenesis of inflammatory diseases as well as malignancies, we investigated gene expression of IL-18 binding protein (IL-18BP) in different human cell systems, namely in the keratinocyte cell line HaCaT, in the colon carcinoma cell line DLD-1, and in primary renal mesangial cells.
We show that deficient IL-18 production occurs at initial inflammation stages of disease, and that IL-1β production is more significantly impaired in Casp11<sup>-/-</sup> colons during established CAC.
The current meta-analysis suggests that the -607C/A polymorphism in IL-18 gene promoter is associated with a significantly increased risk of cancer, especially of breast cancer, nasopharyngeal carcinoma and esophageal cancer and in Asian and Mixed populations.
Increased IL-18 levels in the serum of cancer patients correlated with malignancy, and IL-18 acts a crucial factor for cell migration in gastric cancer and melanoma.
Inflammasomes, which are intracellular multi-protein complexes, promote acute and chronic inflammation via interleukin-1β or interleukin-18 maturation, and they are known targets for metabolic syndromes and cancer.
Short- and long-term administration of interleukin-18 appeared to have no adverse effects on the kidney in these mice, suggesting that administration may be a safe and novel treatment for metabolic diseases and cancer.
An inappropriate production of interleukin-18 (IL-18) contributes to the pathogenesis of malignancies and may influence the clinical outcome of patients.
Single nucleotide polymorphisms in the promoter region of interleukin-18 (IL-18), an inflammatory cytokine, have been linked to susceptibility to many diseases, including cancer and immune dysfunction.
These data indicated that oncolytic adenovirus expressing IL-18 could exert potential antitumor activity via inhibition of angiogenesis and offer a novel approach to cancer therapy.
The association of -137G>C polymorphism in the promoter region of IL-18 with cancer risk is still elusive based on current genetic association studies.
Here, we demonstrate that interleukin-18 (IL-18)-secreting CAR T cells exhibit enhanced in vivo expansion and persistence and significantly increase long-term survival in syngeneic mouse models of both hematological and solid malignancies.
No consensus exists on the impact of polymorphisms in cytokines (such as interleukin IL-8 and IL-18) on cancer risk; moreover, there is very little evidence regarding head and neck cancer (HNC).
We made the following important findings: (1) Caspase-1 exerts its regulatory effects on the majority of genes in a tissue-specific manner; (2) Caspase-1 regulatory genes partially cooperates with genes regulated by sirtuin-1 during organ injury and inflammation in adipose tissue but not in the liver; (3) Caspase-1 cooperates with IL-1β in regulating less than half of the genes involved in cardiovascular disease, organismal injury, and cancer in mouse liver; (4) The meta-analysis identifies 40 caspase-1 globally regulated genes across tissues, suggesting that caspase-1 globally regulates many novel pathways; and (5) The meta-analysis identified new cooperatively and non-cooperatively regulated genes in caspase-1, IL-1β, IL-18, and Sirt-1 pathways.
Several lines of evidence suggests that in cancer the inflammasome is positively associated with characteristics such as elevated levels of IL-1β and IL-18, activation of NF-κB signaling, enhanced mitochondrial oxidative stress, and activation of autophagic process.
The effects of gpIL-12 and gpIL-18 on the tumors implanted in guinea pigs will encourage us to use IL-12- and IL-18-inducible adjuvants for immunotherapy in human patients with solid cancer.
Our pooled analysis supported that IL-18 is a good candidate for large-scale epidemiological case-control studies that may be a low-penetrance susceptibility biomarker for cancer.