Disease relevance of Il18

• Higher IL-18 plasma levels also are associated with restenosis after coronary artery angioplasty performed in patients with acute myocardial infarction [1].
• Role of IL-18 in acute lung inflammation [2].
• These data provide for the first time a mechanism of IL-18-mediated CXCL16 gene transcription and CXCL16-dependent ASMC proliferation and suggest a role for IL-18-CXCL16 cross-talk in atherogenesis and restenosis following angioplasty [3].
• Specific oligonucleotide primers were used to identify and isolate IFN-gamma-inducing factor (IGIF) from the brain of rats with developing experimental autoimmune encephalomyelitis (EAE), a T cell-mediated autoimmune disease of the central nervous system that serves as a model for multiple sclerosis [4].
• Neutralizing antibodies to IFN-gamma-inducing factor prevent experimental autoimmune encephalomyelitis [4].

High impact information on Il18

• The angiostatic effect occurred despite high levels of vascular endothelial growth factor (VEGF), and was associated with down-regulation of the proangiogenic cytokines IL-18, CXCL16, and CXCL5 and up-regulation of the angiogenesis inhibitor endostatin [5].
• When rat lung macrophages, fibroblasts, type II cells, and endothelial cells were cultured in vitro with LPS, only the first two produced IL-18 [2].
• Intratracheal administration of the natural antagonist of IL-18, IL-18 binding protein, resulted in suppressed lung vascular permeability and decreased BAL content of neutrophils, cytokines, and chemokines [2].
• Prominent immunostaining for IL-18 was found in alveolar macrophages from inflamed lungs [2].
• In situ hybridization showed that, in contrast to the adrenal cortex, in spleen and duodenum IL-18 is primarily localized to immune cells [6].

Chemical compound and disease context of Il18

• In vivo, we found that IL-18 expression and Fas expression synergistically inhibited C6 cell tumorigenesis with the glioma cells being subcutaneously injected in rat flank [7].
• Long-lasting gene expression by particle-mediated intramuscular transfection modified with bupivacaine: combinatorial gene therapy with IL-12 and IL-18 cDNA against rat sarcoma at a distant site [8].

Biological context of Il18

• In addition, in vitro data show that IL-18 affects smooth muscle cell proliferation [1].
• BACKGROUND: Studies in humans and animal models suggest that interleukin-18 (IL-18) plays a crucial role in vascular pathologies [1].
• First, we analyzed IL-18 gene expression by reverse transcription-polymerase chain reaction (RT-PCR) in rat thyroid FRTL-5 cells and human thyroid tissue samples [9].
• In the central nervous system, IL-18 was demonstrated to induce sleep and to influence long-term potentiation and was proposed to mediate local inflammatory reactions [10].
• Recombinant IL-18 was seen to stimulate spermatogonial DNA synthesis in cultures of staged segments of rat seminiferous tubules, without influencing germ cell apoptosis [11].

Anatomical context of Il18

• Strong immunoreactivity for IL-18 was detected in the medial smooth muscle cells at days 2 and 7 after balloon injury and in proliferating/migrating smooth muscle cells in neointima at day 14 [1].
• Increased expression of IL-18 and IL-18Ralpha/beta mRNA was detectable in carotid arteries from days 2 to 14 after angioplasty [1].
• Rat brain IL-18 shows close homology to mouse and human IL-18, and to the recently published sequence from the rat adrenal gland [12].
• Interleukin-18 (IL-18) is a pro-inflammatory cytokine predominantly studied as a modulator of immune functions and also produced in the adrenal cortex following activation of the hypothalamic-pituitary-adrenal axis [10].
• This study is the first to demonstrate the detection of IL-18 in the thyroid gland [9].

Associations of Il18 with chemical compounds

• A novel role for IL-18 in corticosterone-mediated intestinal damage in a two-hit rodent model of alcohol intoxication and injury [13].
• Another group of rats was treated with caspase-1 inhibitor Ac-YVAD-CHO to block IL-18 production [13].
• Taken together, these data suggested that the effect of TSH on IL-18 gene expression was mediated by activating protein kinase A. Treatment of FRTL-5 cells with the antithyroid drug, methimazole (MMI), suppressed this stimulatory action of TSH on IL-18 gene expression [9].
• Interestingly, IL-18 was localized mainly to the basal epithelial cells and the infiltrating macrophages in the regressing VP, whereas IL-15 was induced in the luminal epithelium [14].
• The effects of the pro-inflammatory cytokine interleukin-18 (IL-18) were investigated on both normal and isolated N-methyl-D-aspartate (NMDA) receptor-mediated field excitatory post synaptic potentials (fEPSP) and on the induction of long-term potentiation (LTP) in the rat dentate gyrus in vitro [15].

Regulatory relationships of Il18

• We found that IL-18-transduced glioma cells secreted IL-18 and induced PBMC IFN-gamma production in vitro [7].
• TNF-alpha and H2O2 induce IL-18 and IL-18R beta expression in cardiomyocytes via NF-kappa B activation [16].
• We have shown in previous studies that proinflammatory interleukin-18 and interleukin-12 are up-regulated in the ileum of rats with experimental NEC and that epidermal growth factor (EGF) reduces the development of disease [17].

Other interactions of Il18

• This regulation is potentially mediated by milk TGF-beta2, as well as endogenous IL-18 [18].
• We assessed the role of TGF-beta in mediating mucosal immune development and specifically the effect on endogenous IL-18 [18].
• With regard to IFN-gamma-inducing cytokines, we observed enhanced IL-12 mRNA levels in vivo, whereas IL-18 gene expression was slightly decreased [19].
• In conclusion, we demonstrated for the first time that IL-18 is a prohypernociceptive cytokine that induces mechanical hypernociception mediated by endothelin, via ET(B) receptor [20].
• Thus, the activated microglia-derived cytokines, TNF-alpha and IL-18, may either inhibit the neuronal differentiation or induce neuronal cell death in the NPC culture, whereas these cells may also produce factors to improve the neurite branching in the NPC culture [21].

Analytical, diagnostic and therapeutic context of Il18

• ELISA studies confirmed induction of IL-18 in inflamed lungs (in lung homogenates and in BAL fluids) [2].
• Thus, analysis by RT-PCR and Western blotting revealed pronounced testicular expression of pro-IL-18 from postnatal day 5 and onwards [11].
• Expression of both IL-18 mRNA and protein was found to be localised to meiotic and post-meiotic germ cells as evaluated by in situ hybridisation and immunohistochemistry, respectively [11].
• Using immunocytochemistry and in situ hybridization we report the unprecedented localization of IL-18 in the neurons of the superior part of the medial habenula (MHbS), their projections to the interpenducular nucleus and its expression in the ependymal cells surrounding the third and the lateral ventricles [10].
• Northern blot demonstrated that while the adrenal gland synthesized IL-18 mRNA of 1.1 kb, spleen and duodenum produced a 0.9-kb transcript [6].

References