Gene Symbol: Il18
Description: interleukin 18
Alias: IL-18, interleukin-18, IFN-gamma-inducing factor, IL-1 gamma, interferon gamma-inducing factor, interleukin-1 gamma
Species: rat
Products:     Il18

Top Publications

  1. Sugama S, Cho B, Baker H, Joh T, Lucero J, Conti B. Neurons of the superior nucleus of the medial habenula and ependymal cells express IL-18 in rat CNS. Brain Res. 2002;958:1-9 pubmed
    ..They also suggest that ependymal cells may be the source of IL-18 previously reported in the cerebrospinal fluid (CSF). The role of IL-18 in the ependyma and the CSF remains to be elucidated. ..
  2. Hedtjarn M, Leverin A, Eriksson K, Blomgren K, Mallard C, Hagberg H. Interleukin-18 involvement in hypoxic-ischemic brain injury. J Neurosci. 2002;22:5910-9 pubmed
    ..In conclusion, we found that IL-18 expression in microglia was markedly increased after HI and that IL-18 appears to be important for the development of HI brain injury. ..
  3. Culhane A, Hall M, Rothwell N, Luheshi G. Cloning of rat brain interleukin-18 cDNA. Mol Psychiatry. 1998;3:362-6 pubmed
    ..The cytokine interleukin-18 (also called interferon gamma inducing factor, IGIF) was first isolated from the liver of mice during toxic shock...
  4. Kim S, Son J, Yang E, Kim J, Park H. A functional promoter polymorphism of the human IL18 gene is associated with aspirin-induced urticaria. Br J Dermatol. 2011;165:976-84 pubmed publisher
    ..Two promoter polymorphisms of the IL18 gene (-607A/C and -137G/C) were genotyped using the primer extension method...
  5. Hoshino K, Tsutsui H, Kawai T, Takeda K, Nakanishi K, Takeda Y, et al. Cutting edge: generation of IL-18 receptor-deficient mice: evidence for IL-1 receptor-related protein as an essential IL-18 binding receptor. J Immunol. 1999;162:5041-4 pubmed
    ..Th1 cell development was also impaired in IL-1Rrp-deficient mice. These data demonstrate that IL-1Rrp is a ligand-binding receptor that is essential for IL-18-mediated signaling events. ..
  6. van de Wetering D, de Paus R, van Dissel J, van de Vosse E. IL-23 modulates CD56+/CD3- NK cell and CD56+/CD3+ NK-like T cell function differentially from IL-12. Int Immunol. 2009;21:145-53 pubmed publisher
  7. Ohkusu K, Yoshimoto T, Takeda K, Ogura T, Kashiwamura S, Iwakura Y, et al. Potentiality of interleukin-18 as a useful reagent for treatment and prevention of Leishmania major infection. Infect Immun. 2000;68:2449-56 pubmed
    ..Our results also indicate the high potentiality of IL-18 as a useful reagent for treatment as well as prevention against reinfection. ..
  8. Melnikov V, Ecder T, Fantuzzi G, Siegmund B, Lucia M, Dinarello C, et al. Impaired IL-18 processing protects caspase-1-deficient mice from ischemic acute renal failure. J Clin Invest. 2001;107:1145-52 pubmed
    ..Finally, we confirmed histologically that caspase-1(-/-) mice show decreased neutrophil infiltration, indicating that the deleterious role of IL-18 in ischemic ARF may be due to increased neutrophil infiltration. ..
  9. Yamanaka K, Clark R, Dowgiert R, Hurwitz D, Shibata M, Rich B, et al. Expression of interleukin-18 and caspase-1 in cutaneous T-cell lymphoma. Clin Cancer Res. 2006;12:376-82 pubmed

More Information


  1. Imboden M, Nicod L, Nieters A, Glaus E, Matyas G, Bircher A, et al. The common G-allele of interleukin-18 single-nucleotide polymorphism is a genetic risk factor for atopic asthma. The SAPALDIA Cohort Study. Clin Exp Allergy. 2006;36:211-8 pubmed
    ..029). None of 74 incident asthma cases with atopy at baseline exhibited the CC genotype. Our results strongly suggest that this variant of the IL-18 gene is an important genetic determinant involved in the development of atopic asthma. ..
  2. Jordan J, Guo R, Yun E, Sarma V, Warner R, Crouch L, et al. Role of IL-18 in acute lung inflammation. J Immunol. 2001;167:7060-8 pubmed
    ..These findings suggest that endogenous IL-18 functions as a proinflammatory cytokine in this model of acute lung inflammation, serving as an autocrine activator to bring about expression of other inflammatory mediators. ..
  3. Jander S, Schroeter M, Stoll G. Interleukin-18 expression after focal ischemia of the rat brain: association with the late-stage inflammatory response. J Cereb Blood Flow Metab. 2002;22:62-70 pubmed
  4. Sifringer M, Stefovska V, Endesfelder S, Stahel P, Genz K, Dzietko M, et al. Activation of caspase-1 dependent interleukins in developmental brain trauma. Neurobiol Dis. 2007;25:614-22 pubmed
    ..These findings indicate that IL-18 is involved in trauma-induced neuronal cell death in the immature rodent brain and might serve as a potential therapeutic target. ..
  5. Micallef M, Ohtsuki T, Kohno K, Tanabe F, Ushio S, Namba M, et al. Interferon-gamma-inducing factor enhances T helper 1 cytokine production by stimulated human T cells: synergism with interleukin-12 for interferon-gamma production. Eur J Immunol. 1996;26:1647-51 pubmed
    ..Based on structural and functional differences from any known cytokines, it was recently proposed that this cytokine be designated interleukin-18. ..
  6. Vasudeva K, Vodovotz Y, Azhar N, Barclay D, Janjic J, Pollock J. In vivo and systems biology studies implicate IL-18 as a central mediator in chronic pain. J Neuroimmunol. 2015;283:43-9 pubmed publisher
    ..Immunofluorescence supported a role for inflammasome activation and induction of IL-18 at the site of injury. Combined in vivo and in silico approaches may thus highlight novel targets in peripheral neuropathy. ..
  7. Bossù P, Cutuli D, Palladino I, Caporali P, Angelucci F, Laricchiuta D, et al. A single intraperitoneal injection of endotoxin in rats induces long-lasting modifications in behavior and brain protein levels of TNF-? and IL-18. J Neuroinflammation. 2012;9:101 pubmed
    ..This leads to speculation that, though with still unclear mechanisms, both cytokines might take part in long-lasting modifications of brain functions, including behavioral alteration. ..
  8. Tucci M, Quatraro C, Dammacco F, Silvestris F. Interleukin-18 overexpression as a hallmark of the activity of autoimmune inflammatory myopathies. Clin Exp Immunol. 2006;146:21-31 pubmed
    ..Measurement of IL-18 may thus predict the severity of both DM and PM. ..
  9. Harker J, Godlee A, Wahlsten J, Lee D, Thorne L, Sawant D, et al. Interleukin 18 coexpression during respiratory syncytial virus infection results in enhanced disease mediated by natural killer cells. J Virol. 2010;84:4073-82 pubmed publisher
    ..We therefore constructed a recombinant RSV expressing murine interleukin 18 (RSV/IL-18), a cytokine capable of inducing strong antiviral immune responses...
  10. Rovina N, Dima E, Gerassimou C, Kollintza A, Gratziou C, Roussos C. Interleukin-18 in induced sputum: association with lung function in chronic obstructive pulmonary disease. Respir Med. 2009;103:1056-62 pubmed publisher
    ..In patients with COPD, increased levels of IL-18 in induced sputum were associated with airflow limitation, suggesting that IL-18 may be implicated in the pathogenesis of COPD. ..
  11. Shi B, Ni Z, Cao L, Zhou M, Mou S, Wang Q, et al. Serum IL-18 is closely associated with renal tubulointerstitial injury and predicts renal prognosis in IgA nephropathy. Mediators Inflamm. 2012;2012:728417 pubmed publisher
    ..03), and Cox analysis further confirmed that serum IL-18 levels were an independent predictor of renal prognosis (? = 1.98, P = 0.003). ..
  12. Khan D, Ansari W, Khan F. Pro/anti-inflammatory cytokines in the pathogenesis of premature coronary artery disease. J Interferon Cytokine Res. 2011;31:561-7 pubmed publisher
    ..01) with the degree of angiographic blockade. Pro/anti-inflammatory cytokines play a vital role in the pathogenesis of PCAD and have potential to identify the degree of atherosclerosis. ..
  13. Gono T, Kawaguchi Y, Sugiura T, Ichida H, Takagi K, Katsumata Y, et al. Interleukin-18 is a key mediator in dermatomyositis: potential contribution to development of interstitial lung disease. Rheumatology (Oxford). 2010;49:1878-81 pubmed publisher
    ..To determine whether IL-18 is involved in the inflammation of DM and PM...
  14. Lim A, Allison C, Tan D, Oliver B, Price P, Waterer G. Immunological markers of lung disease due to non-tuberculous mycobacteria. Dis Markers. 2010;29:103-9 pubmed publisher
    ..Compared with responders, patients who responded poorly to treatment generally had higher plasma levels of CXCL10 and IL-18, and higher frequencies of activated CD8(+) T cells. ..
  15. Skopinski P, Rogala E, Duda Król B, Lipinska A, Sommer E, Chorostowska Wynimko J, et al. Increased interleukin-18 content and angiogenic activity of sera from diabetic (Type 2) patients with background retinopathy. J Diabetes Complications. 2005;19:335-8 pubmed
    ..Sera from both groups of people after neutralization with antihuman IL-18 antibodies lost substantial part of their angiogenic activity. ..
  16. del Rey A, Balschun D, Wetzel W, Randolf A, Besedovsky H. A cytokine network involving brain-borne IL-1?, IL-1ra, IL-18, IL-6, and TNF? operates during long-term potentiation and learning. Brain Behav Immun. 2013;33:15-23 pubmed publisher
    ..Taken together with previous studies, we conclude that activation of a cytokine network in the brain is a physiologic relevant phenomenon not only for LTP maintenance but also for certain types of learning. ..
  17. Strand M, Wahlgren A, Svechnikov K, Zetterström C, Setchell B, Soder O. Interleukin-18 is expressed in rat testis and may promote germ cell growth. Mol Cell Endocrinol. 2005;240:64-73 pubmed
    ..These results suggest that IL-18 may have host-protective and growth-promoting functions in the testis, but further investigations need to be done to confirm this. ..
  18. Garcia G, Xia Y, Ku G, Johnson R, Wilson C, Feng L. IL-18 translational inhibition restricts IFN-gamma expression in crescentic glomerulonephritis. Kidney Int. 2003;64:160-9 pubmed
    ..Furthermore, it was suggested that possible IL-18/IFN-gamma induction of local proliferation of macrophages and CD8+ cells might be an important mechanism for amplifying CD8+-mediated macrophage-dependent GN. ..
  19. Takeuchi D, Yoshidome H, Kurosawa H, Kimura F, Shimizu H, Ohtsuka M, et al. Interleukin-18 exacerbates pulmonary injury after hepatic ischemia/reperfusion in mice. J Surg Res. 2010;158:87-93 pubmed publisher
    ..The data suggested that IL-18 plays an important role in the development of pulmonary injury after hepatic ischemia/reperfusion by up-regulating proinflammatory mediators and possibly suppressing anti-inflammatory cytokine expression. ..
  20. Chandrasekar B, Colston J, de la Rosa S, Rao P, Freeman G. TNF-alpha and H2O2 induce IL-18 and IL-18R beta expression in cardiomyocytes via NF-kappa B activation. Biochem Biophys Res Commun. 2003;303:1152-8 pubmed
    ..Presence of both ligand and receptors suggests IL-18 impacts myocardial biology through an autocrine pathway. ..
  21. Ragab D, Abdallah D, El Abhar H. Cilostazol renoprotective effect: modulation of PPAR-?, NGAL, KIM-1 and IL-18 underlies its novel effect in a model of ischemia-reperfusion. PLoS ONE. 2014;9:e95313 pubmed publisher
  22. Menge T, Jander S, Stoll G. Induction of the proinflammatory cytokine interleukin-18 by axonal injury. J Neurosci Res. 2001;65:332-9 pubmed
  23. Li W, Guo T, Liang D, Shi X, Wei T, Kingery W, et al. The NALP1 inflammasome controls cytokine production and nociception in a rat fracture model of complex regional pain syndrome. Pain. 2009;147:277-86 pubmed publisher
    ..These findings highlight the possible importance of neuro-cutaneous signaling and innate immunity mechanisms in the development of CRPS...
  24. Plitz T, Saint Mezard P, Satho M, Herren S, Waltzinger C, De Carvalho Bittencourt M, et al. IL-18 binding protein protects against contact hypersensitivity. J Immunol. 2003;171:1164-71 pubmed
    ..Taken together with the evidence that IL-18 is present in tissue samples of the human disease, our data reinforces IL-18BP as a candidate for this therapeutic indication. ..
  25. Jung H, Ryu H, Kim M, Kim W, Choi H, Choi H, et al. Interleukin-18 attenuates disruption of brain-blood barrier induced by status epilepticus within the rat piriform cortex in interferon-? independent pathway. Brain Res. 2012;1447:126-34 pubmed publisher
    ..Therefore, our findings suggest that IL-18 may have protective effect on SE-induced BBB disruption in IFN-? independent mechanism. ..
  26. Zhang R, Zhang X, Zhang J, Wu J, Ye Q, Xu R, et al. Efficacy and mechanism of Salvia miltiorrhizae injection in the treatment of rats with severe acute pancreatitis. Inflammation. 2009;32:109-19 pubmed publisher
  27. Lindegaard B, Hansen A, Pilegaard H, Keller P, Gerstoft J, Pedersen B. Adipose tissue expression of IL-18 and HIV-associated lipodystrophy. AIDS. 2004;18:1956-8 pubmed
    ..Higher levels of IL-18 mRNA were found in femoral-gluteal AT compared with abdominal AT, and correlated with limb fat loss. These findings suggest that IL-18 is linked to HIV-associated lipodystrophy. ..
  28. Zhang J, Liang R, Wang L, Yan R, Hou R, Gao S, et al. Effects of an aqueous extract of Crataegus pinnatifida Bge. var. major N.E.Br. fruit on experimental atherosclerosis in rats. J Ethnopharmacol. 2013;148:563-9 pubmed publisher
    ..The aim of the study is to investigate the effect and possible mechanisms of the aqueous extract of Crataegus pinnatifida var. major on AS rats...
  29. Lian H, Jin N, Li X, Mi Z, Zhang J, Sun L, et al. Induction of an effective anti-tumor immune response and tumor regression by combined administration of IL-18 and Apoptin. Cancer Immunol Immunother. 2007;56:181-92 pubmed
    ..These results demonstrate that vaccination with Apoptin together with IL-18 may be a novel and powerful strategy for cancer immunotherapy. ..
  30. Li X, Kovacs E, Schwacha M, Chaudry I, Choudhry M. Acute alcohol intoxication increases interleukin-18-mediated neutrophil infiltration and lung inflammation following burn injury in rats. Am J Physiol Lung Cell Mol Physiol. 2007;292:L1193-201 pubmed
    ..Furthermore, the presence of neutrophils appears to be critical for IL-18-meditaed increased lung tissue edema following a combined insult of EtOH and burn injury. ..
  31. Wang L, Gong B, Zhu L, Zhuo L, Li X, Zhang Q, et al. [Influence of electroacupuncture stimulation on serum and hepatic interleukin-18 expression in nonalcoholic fatty liver rats]. Zhen Ci Yan Jiu. 2013;38:208-13 pubmed
  32. Chooklin S. Pathogenic aspects of pulmonary complications in acute pancreatitis patients. Hepatobiliary Pancreat Dis Int. 2009;8:186-92 pubmed
    ..At IL-18 concentrations >650 pg/ml, AP patients are likely to develop pulmonary dysfunction (sensitivity 58%, specificity 100%, LR-positive >58) which allows us to use it as a screening test. ..
  33. Cardenas S, Scuri M, Samsell L, Ducatman B, Bejarano P, Auais A, et al. Neurotrophic and neuroimmune responses to early-life Pseudomonas aeruginosa infection in rat lungs. Am J Physiol Lung Cell Mol Physiol. 2010;299:L334-44 pubmed publisher
    ..Our data suggest that neurogenic-mediated immunoinflammatory mechanisms play important roles in airway inflammation and hyperreactivity associated with P. aeruginosa when infection occurs early in life. ..
  34. Baldini C, Rossi C, Ferro F, Santini E, Seccia V, Donati V, et al. The P2X7 receptor-inflammasome complex has a role in modulating the inflammatory response in primary Sjögren's syndrome. J Intern Med. 2013;274:480-9 pubmed publisher
    ..This finding provides the basis for studying the complex mechanisms underlying pSS, as well as for developing novel potential therapeutic strategies. ..
  35. Nagai H, Hara I, Horikawa T, Oka M, Kamidono S, Ichihashi M. Gene transfer of secreted-type modified interleukin-18 gene to B16F10 melanoma cells suppresses in vivo tumor growth through inhibition of tumor vessel formation. J Invest Dermatol. 2002;119:541-8 pubmed
    ..was markedly reduced and that necrosis was extensively induced in interleukin-18-secreting B16F10 melanoma (B16/IL18) tissues, whereas abundant tumor vessel formation was observed in B16/IL18 tissues of interferon-gamma-neutralized ..
  36. Watanabe T, Kitani A, Murray P, Wakatsuki Y, Fuss I, Strober W. Nucleotide binding oligomerization domain 2 deficiency leads to dysregulated TLR2 signaling and induction of antigen-specific colitis. Immunity. 2006;25:473-85 pubmed
    ..Thus, NOD2-deficient mice become susceptible to colitis as a result of increased TLR2 responses when they have the capacity to respond to an antigen expressed by mucosal bacteria. ..
  37. Okano F, Satoh M, Ido T, Yamada K. Cloning of cDNA for canine interleukin-18 and canine interleukin-1beta converting enzyme and expression of canine interleukin-18. J Interferon Cytokine Res. 1999;19:27-32 pubmed
    ..Canine IL-18 and canine IL-12 produced canine IFN-gamma synergistically. Canine IL-18 suppressed the growth of tumor cells transplanted in SCID mice. Cloned canine IL-18 should prove useful as an anticancer agent. ..
  38. Kalina U, Kauschat D, Koyama N, Nuernberger H, Ballas K, Koschmieder S, et al. IL-18 activates STAT3 in the natural killer cell line 92, augments cytotoxic activity, and mediates IFN-gamma production by the stress kinase p38 and by the extracellular regulated kinases p44erk-1 and p42erk-21. J Immunol. 2000;165:1307-13 pubmed
    ..In contrast, proliferation of NK92 cells is not affected by MAPK p44erk-1 and p42erk-2. ..
  39. Lee H, Park S, Chung S, Woo J, Chae S, Lee S, et al. Interleukin-18/-607 gene polymorphism in allergic rhinitis. Int J Pediatr Otorhinolaryngol. 2006;70:1085-8 pubmed
    ..05). The A allele in the IL-18/-607 gene promoter region may be involved in the development of allergic rhinitis in the Korean population. ..
  40. Yamagata S, Tomita K, Sato R, Niwa A, Higashino H, Tohda Y. Interleukin-18-deficient mice exhibit diminished chronic inflammation and airway remodelling in ovalbumin-induced asthma model. Clin Exp Immunol. 2008;154:295-304 pubmed publisher
    ..These findings suggest that IL-18 may enhance chronic airway inflammation and airway remodelling through the production of IFN-gamma, IL-13 and TGF-beta1 in the OVA-induced asthma mouse model. ..
  41. Miyauchi S, Matsuura B, Ueda T, Eguchi T, Tamaru M, Yamamoto S, et al. Interleukin-18 induces insulin resistance in the hyperthyroid state. Endocr J. 2013;60:449-55 pubmed
    ..Insulin resistance increased in experimental hyperthyroid mice and IL-18-injected mice. These findings suggest IL-18 to be an important factor inducing insulin resistance in hyperthyroidism. ..
  42. Smaldone M, Vodovotz Y, Tyagi V, Barclay D, Philips B, Yoshimura N, et al. Multiplex analysis of urinary cytokine levels in rat model of cyclophosphamide-induced cystitis. Urology. 2009;73:421-6 pubmed publisher
    ..Additional delineation of urine and bladder tissue cytokine expression might yield biomarkers for cystitis. ..
  43. Kawase Y, Hoshino T, Yokota K, Kuzuhara A, Kirii Y, Nishiwaki E, et al. Exacerbated and prolonged allergic and non-allergic inflammatory cutaneous reaction in mice with targeted interleukin-18 expression in the skin. J Invest Dermatol. 2003;121:502-9 pubmed
    b>Interleukin 18 induces both T helper 1 and T helper 2 cytokines, proinflammatory cytokines, chemokines, and IgE and IgG1 production. A role of interleukin 18 in inflammatory cutaneous reactions is still unclear, however...
  44. Shimizu M, Yokoyama T, Yamada K, Kaneda H, Wada H, Wada T, et al. Distinct cytokine profiles of systemic-onset juvenile idiopathic arthritis-associated macrophage activation syndrome with particular emphasis on the role of interleukin-18 in its pathogenesis. Rheumatology (Oxford). 2010;49:1645-53 pubmed publisher
    ..The cytokine release pattern in MAS/HLH is different among patients with different aetiologies. Monitoring the cytokine profile, including IL-18, may be useful for differentiation of MAS/HLH and evaluation of disease activity in s-JIA. ..
  45. Nagai N, Murao T, Ito Y, Okamoto N, Okamura H. Involvement of interleukin 18 in lens opacification of Otsuka Long-Evans Tokushima Fatty rats, a model of human type 2 diabetes. Curr Eye Res. 2011;36:497-506 pubmed publisher
    Mature interleukin 18 (IL-18) leads to the production of interferon-?, nuclear factor kappa B, and inducible nitric oxide synthase, and we previously reported that the enhancement of IL-18 in lens of hereditary cataract model rats was ..
  46. Ye X, Tang B, Ma Z, Zhou J, Myers L, Kang A, et al. The effects of interleukin-18 on rat articular chondrocytes: a study of mRNA expression and protein synthesis of proinflammatory substances. Clin Exp Immunol. 2007;149:553-60 pubmed
    ..These findings suggest further that IL-18 antagonists might prove beneficial as anti-inflammatory and chondroprotective agents in the treatment of arthritis, and that the development of such agents for human use is worth consideration...
  47. Akhtar S, Li X, Kovacs E, Gamelli R, Choudhry M. Interleukin-18 delays neutrophil apoptosis following alcohol intoxication and burn injury. Mol Med. 2011;17:88-94 pubmed publisher
    ..These findings suggest that IL-18 delays neutrophil apoptosis following EtOH and burn injury by modulating the pro- and antiapoptotic proteins. ..
  48. Wan X, Fan L, Hu B, Yang J, Li X, Chen X, et al. Small interfering RNA targeting IKK? prevents renal ischemia-reperfusion injury in rats. Am J Physiol Renal Physiol. 2011;300:F857-63 pubmed publisher
    ..Consequently, our data confirm that targeted silencing of IKK? using siRNA substantially diminishes kidney injury and inflammation following ischemia-reperfusion. ..
  49. Chen J, Tsai C, Lin H, Huang C, Leung Y, Lai S, et al. Interlukin-18 Is a Pivot Regulatory Factor on Matrix Metalloproteinase-13 Expression and Brain Astrocytic Migration. Mol Neurobiol. 2016;53:6218-6227 pubmed publisher
    ..These findings also indicate that IL-18 is an important regulator leading to MMP-13 expression and cell migration in astrocytes. ..
  50. Haznedaroglu S, Ozturk M, Sancak B, Goker B, Onat A, Bukan N, et al. Serum interleukin 17 and interleukin 18 levels in familial Mediterranean fever. Clin Exp Rheumatol. 2005;23:S77-80 pubmed
    ..05). Our data suggest that IL-17 and IL-18 contribute to the cytokine network in the inflammatory cascade of FMF. However, their roles for the initiation of FMF attacks remain to be established. ..
  51. Shao P, Chiu C, Yuen C, Chua S, Chang L, Sheu J, et al. Shock wave therapy effectively attenuates inflammation in rat carotid artery following endothelial denudation by balloon catheter. Cardiology. 2010;115:130-44 pubmed publisher
    ..001). ECSW markedly attenuates inflammatory responses, proliferation of neointima and smooth muscle cells in a rat vascular injury model. ..
  52. Kieszko R, Krawczyk P, Jankowska O, Chocholska S, Krol A, Milanowski J. The clinical significance of interleukin 18 assessment in sarcoidosis patients. Respir Med. 2007;101:722-8 pubmed
    ..The cytokine profile in inflamed lesions of sarcoidosis is mainly determined by T helper 1 (Th1) cells. Interleukin 18 (IL-18) is primarily a monocyte/macrophage-derived cytokine...
  53. Mysliwiec J, Kretowski A, Stepien A, Mironczuk K, Kinalska I. Interleukin 18 and transforming growth factor beta1 in the serum of patients with Graves' ophthalmopathy treated with corticosteroids. Int Immunopharmacol. 2003;3:549-52 pubmed
    ..Our results suggest that efficient corticosteroid therapy in patients with Graves' ophthalmopathy may be related to its influence on systemic IL-18. ..
  54. Sugama S, Kim Y, Baker H, Tinti C, Kim H, Joh T, et al. Tissue-specific expression of rat IL-18 gene and response to adrenocorticotropic hormone treatment. J Immunol. 2000;165:6287-92 pubmed
    ..These results demonstrate tissue-specific expression and promoter usage of IL-18 gene and suggest that the adrenal cortex and not immune cells may be the source of IL-18 during stress. ..
  55. Reyes L, Reinhard M, Brown M. Different inflammatory responses are associated with Ureaplasma parvum-induced UTI and urolith formation. BMC Infect Dis. 2009;9:9 pubmed publisher
    ..Animals were inoculated with sterile broth, 10(1), 10(3), 10(5), 10(7), or 10(9) log CFU of a rat-adapted strain of Ureaplasma parvum...
  56. Xu J, Treem W, Roman C, Anderson V, Rubenstein R, Schwarz S. Ileal immune dysregulation in necrotizing enterocolitis: role of CD40/CD40L in the pathogenesis of disease. J Pediatr Gastroenterol Nutr. 2011;52:140-6 pubmed publisher
    ..Dampened CD40 signaling may be related to enhanced IL-10 expression and a suppressed T-cell response to injury. We speculate that augmenting CD40-CD40L interactions may achieve a protective effect in this NEC model. ..
  57. Lee Y, Kang S, Park J, Bae Y, Lee E, Lee E, et al. Interleukin-18 promoter polymorphisms in patients with Behçet's disease. Hum Immunol. 2006;67:812-8 pubmed
    ..034 by ANOVA; p = 0.009 by t-test, respectively) than those with other genotypes or diplotypes. These results suggest that the IL-18 promoter gene is a candidate susceptibility gene in BD patients. ..
  58. Kinoshita M, Miyazaki H, Ono S, Inatsu A, Nakashima H, Tsujimoto H, et al. Enhancement of neutrophil function by interleukin-18 therapy protects burn-injured mice from methicillin-resistant Staphylococcus aureus. Infect Immun. 2011;79:2670-80 pubmed publisher
    ..Thus, although neutrophil functions were impaired in burn-injured mice, IL-18 therapy markedly activated neutrophil functions, thereby increasing survival from postburn MRSA infection. ..
  59. Mo J, Bai B, Li Y, Deng J, Zhang S, Chen Y, et al. Expression of interleukin-18 in a rat model of deep vein thrombosis. J Cardiovasc Surg (Torino). 2012;53:625-30 pubmed
    ..Serum IL-18 level increased in the process of DVT, which might impair venous endothelial cells and result in venous thrombosis. IL-18 might be a new potential therapeutic target of DVT prevention. ..
  60. Palomino Morales R, Vazquez Rodriguez T, Torres O, Morado I, Castañeda S, Miranda Filloy J, et al. Association between IL-18 gene polymorphisms and biopsy-proven giant cell arteritis. Arthritis Res Ther. 2010;12:R51 pubmed publisher
    The objective was to investigate the potential implication of the IL18 gene promoter polymorphisms in the susceptibility to giant-cell arteritis (GCA). In total, 212 patients diagnosed with biopsy-proven GCA were included in this study...
  61. Castelar L, Silva M, Castelli E, Deghaide N, Mendes Junior C, Machado A, et al. Interleukin-18 and interferon-gamma polymorphisms in Brazilian human immunodeficiency virus-1-infected patients presenting with lipodystrophy syndrome. Tissue Antigens. 2010;76:126-30 pubmed publisher
    ..The -137G/-607C haplotype was associated with protection against LS. These results indicate that the -607(C/A) SNP is associated with LS development in HIV-infected patients. ..
  62. Akgun M, Saglam L, Kaynar H, Yildirim A, Mirici A, Gorguner M, et al. Serum IL-18 levels in tuberculosis: comparison with pneumonia, lung cancer and healthy controls. Respirology. 2005;10:295-9 pubmed
  63. Wildbaum G, Youssef S, Grabie N, Karin N. Neutralizing antibodies to IFN-gamma-inducing factor prevent experimental autoimmune encephalomyelitis. J Immunol. 1998;161:6368-74 pubmed
    ..Thus, we suggest that perturbation of the Th1/Th2 balance toward Th2 cells is the mechanism underlying EAE blockade by anti-IGIF immunotherapy. ..
  64. Sekine K, Fujishima S, Sasaki J, Ishizaka A, Aiso S, Aikawa N. In vivo IL-18 supplementation ameliorates lethal acute lung injury in burn-primed endotoxemic mice: a novel anti-inflammatory role of IL-18. Shock. 2009;32:554-62 pubmed publisher
  65. Huang X, McClellan S, Barrett R, Hazlett L. IL-18 contributes to host resistance against infection with Pseudomonas aeruginosa through induction of IFN-gamma production. J Immunol. 2002;168:5756-63 pubmed
    ..These data provide evidence that IL-18 contributes to the resistance response by induction of IFN-gamma and that IFN-gamma is required for bacterial killing. ..
  66. Zhang J, Ma C, Liu Y, Yang G, Jiang Y, Xu C. Interleukin 18 accelerates the hepatic cell proliferation in rat liver regeneration after partial hepatectomy. Gene. 2014;537:230-7 pubmed publisher
    b>Interleukin 18 (IL-18) is a proinflammatory cytokine with an ability to accelerate cell proliferation through activating other factors. However, little is yet understood of the role of IL-18 in the regulation of liver regeneration (LR)...
  67. Kuwahara Otani S, Maeda S, Kobayashi K, Minato Y, Tanaka K, Yamanishi K, et al. Interleukin-18 and its receptor are expressed in gonadotropin-releasing hormone neurons of mouse and rat forebrain. Neurosci Lett. 2017;650:33-37 pubmed publisher
    ..These observations suggest that IL-18 exerts direct effects upon the GnRH neuron via IL-18R? and acts on GnRH neurons through an autocrine or paracrine pathway. ..
  68. Xing S, Bi X, Tan H, Zhang Y, Xing Q, Zhang W. Overexpression of interleukin-18 aggravates cardiac fibrosis and diastolic dysfunction in fructose-fed rats. Mol Med. 2010;16:465-70 pubmed publisher
    ..Overexpression of IL-18 leads to aggravated LV remodeling and dysfunction in FFRs. Attenuation of the inflammatory process may provide a novel therapeutic strategy in treating metabolic cardiomyopathy. ..
  69. Chen S, Xu L, Tang J. Association of interleukin 18 gene polymorphism with susceptibility to the development of acute lung injury after cardiopulmonary bypass surgery. Tissue Antigens. 2010;76:245-9 pubmed publisher
    ..b>Interleukin 18 (IL-18) is a potent activator and inducer of accumulating neutrophils in lung, and higher IL-18 level has been ..
  70. Blease K, Kunkel S, Hogaboam C. IL-18 modulates chronic fungal asthma in a murine model; putative involvement of Toll-like receptor-2. Inflamm Res. 2001;50:552-60 pubmed
    ..IL-18 modulates the innate immune response against A. fumigatus conidia and prevents the development of severe fungus-induced asthmatic disease. ..
  71. Hamzaoui A, Ghrairi H, Ammar J, Zekri S, Guemira F, Hamzaoui K. IL-18 mRNA expression and IFN-gamma induction in bronchoalveolar lavage from Behçet's disease. Clin Exp Rheumatol. 2003;21:S8-14 pubmed
    ..Our data indicate that IL-18 up-regulation is a feature of BD and suggest that IL-18 and IFN-gamma may contribute to the local inflammatory response in BD. ..
  72. Ecelbarger C, Rash A, Sinha R, Tiwari S. The effect of chronic candesartan therapy on the metabolic profile and renal tissue cytokine levels in the obese Zucker rat. Mediators Inflamm. 2010;2010:841343 pubmed publisher
    ..Reduced plasma triglycerides and/or renal MCP-1 and IL-1beta may have had a role in this protection. However, these effects were clearly independent of any improvement in glucose tolerance. ..
  73. Jander S, Stoll G. Differential induction of interleukin-12, interleukin-18, and interleukin-1beta converting enzyme mRNA in experimental autoimmune encephalomyelitis of the Lewis rat. J Neuroimmunol. 1998;91:93-9 pubmed
    ..Our data implicate the IL-18/ICE pathway in the amplification of Th1-mediated immune responses in the CNS but suggest a different, so far undefined role of endogenous IL-12 in the late effector phase of EAE. ..
  74. Dzietko M, Hahnemann M, Polley O, Sifringer M, Felderhoff Mueser U, Bührer C. Effects of PMA (PHORBOL-12-MYRISTATE-13-ACETATE) on the Developing Rodent Brain. Biomed Res Int. 2015;2015:318306 pubmed publisher
    ..Mice deficient in IL-18 or IRAK-4 were protected against PMA induced brain injury. PMA treatment during a vulnerable period can alter brain development. IL-18 and IRAK-4 appear to be important for the development of PMA induced injury. ..
  75. Ye X, Tang B, Ma Z, Kang A, Myers L, Cremer M. The roles of interleukin-18 in collagen-induced arthritis in the BB rat. Clin Exp Immunol. 2004;136:440-7 pubmed
    ..Neutralizing endogenous IL-18 with antibodies attenuated CIA, CII immunity and cytokine responses. These studies support the use of IL-18 antagonists as treatments for inflammatory arthritis. ..
  76. Xu B, Aoyama K, Yu S, Kitani A, Okamura H, Kurimoto M, et al. Expression of interleukin-18 in murine contact hypersensitivity. J Interferon Cytokine Res. 1998;18:653-9 pubmed
    ..The present study suggests that IL-18 may be implicated in the pathogenesis of murine CH. ..
  77. Nagai N, Ogata F, Kawasaki N, Ito Y. Increased Expression of Interleukin-18 in Lenses of Ovariectomized Rats. Biol Pharm Bull. 2016;39:138-42 pubmed publisher
    ..These findings support those of previous studies that assessed lens opacification in postmenopausal women. ..
  78. Zhang D, Feng H, Chen W. Effects of hydrogen-rich saline on taurocholate-induced acute pancreatitis in rat. Evid Based Complement Alternat Med. 2013;2013:731932 pubmed publisher
    ..In conclusion, intravenous hydrogen-rich saline injections could attenuate the severity of AP, probably via inhibiting the oxidative stress and reducing the presence of inflammatory mediators. ..
  79. Wang L, Wang L, Chen H, Fan C, Li X, He C, et al. Ethyl pyruvate protects against experimental acute-on-chronic liver failure in rats. World J Gastroenterol. 2012;18:5709-18 pubmed publisher
    ..17, P < 0.0001). EP administration can protect against ACLF in rats, and is a potential and novel therapeutic agent for severe liver injury. ..
  80. Xu G, Jiang X, Xu Y, Zhang J, Huang F, Chen Z, et al. Adenoviral-mediated interleukin-18 expression in mesenchymal stem cells effectively suppresses the growth of glioma in rats. Cell Biol Int. 2009;33:466-74 pubmed publisher
    ..Thus, IL-18 may be an effective adoptive immunotherapy for malignant glioma. When used in conjunction with MSCs as targeting vehicles in vivo, IL-18 may offer a promising new treatment option for malignant glioma. ..
  81. Daigo E, Sakuma Y, Miyoshi K, Noguchi K, Kotani J. Increased expression of interleukin-18 in the trigeminal spinal subnucleus caudalis after inferior alveolar nerve injury in the rat. Neurosci Lett. 2012;529:39-44 pubmed publisher
    ..Our findings are the first report that injury of trigeminal nerve induced IL-18 upregulation in activated microglia in the Vc, suggesting a possible role of IL-18 in orofacial neuropathic pain. ..
  82. Brieland J, Jackson C, Hurst S, Loebenberg D, Muchamuel T, Debets R, et al. Immunomodulatory role of endogenous interleukin-18 in gamma interferon-mediated resolution of replicative Legionella pneumophila lung infection. Infect Immun. 2000;68:6567-73 pubmed
    ..Taken together, these results demonstrate that IL-18 plays a key role in modulating induction of IFN-gamma in the lung in response to L. pneumophila and that together with IL-12, IL-18 regulates intrapulmonary growth of the bacteria. ..
  83. Zhou J, Ping F, Lv W, Feng J, Shang J. Interleukin-18 directly protects cortical neurons by activating PI3K/AKT/NF-?B/CREB pathways. Cytokine. 2014;69:29-38 pubmed publisher
    ..These results in vitro showed the protection of IL-18 on cortical neurons. And this direct neuroprotective effect of IL-18 is crippled by PI3K inhibitor wortmannin. ..
  84. Li C, Zhang X, Liu H, Wang Z, Yin K. Association among plasma interleukin-18 levels, carotid intima- media thickness and severity of obstructive sleep apnea. Chin Med J (Engl). 2009;122:24-9 pubmed
    ..Inflammatory response associated with OSAHS may be related to the development of AS. By improving AHI, miniSaO(2), and reducing plasma IL-18 levels, CPAP treatment may slow down or prevent the development of AS in OSAHS patients. ..
  85. Sohn M, Lee K, Kim K. Interleukin-18 is associated with increased severity of atopic dermatitis in children. Allergy Asthma Proc. 2004;25:181-4 pubmed
    ..There were significant differences in the concentrations of IL-10, IL-12, and soluble Fas ligand between AD patients and normal controls. In conclusion, increased serum IL-18 concentrations may be involved in the pathogenesis of AD. ..
  86. Hoshino T, Wiltrout R, Young H. IL-18 is a potent coinducer of IL-13 in NK and T cells: a new potential role for IL-18 in modulating the immune response. J Immunol. 1999;162:5070-7 pubmed
    ..Thus, depending upon the cell type, IL-18 may act as a strong coinducer of Th1 or Th2 cytokines. Our findings suggest that IL-12 and IL-18 have different roles in the regulation of gene expression in NK and T cells. ..
  87. Tan H, Liu X, Bi X, Xing S, Li L, Gong H, et al. IL-18 overexpression promotes vascular inflammation and remodeling in a rat model of metabolic syndrome. Atherosclerosis. 2010;208:350-7 pubmed publisher
    ..Targeting expression of IL-18 or its specific downstream mediators may retard the progression of MetS and its complications. ..
  88. Lee C, Lin W, Wan L, Tsai Y, Tsai C, Huang C, et al. Association of interleukin-18 gene polymorphism with asthma in Chinese patients. J Clin Lab Anal. 2008;22:39-44 pubmed publisher
    ..We concluded that Chinese who carry the C/C homozygote of the IL-18-105A/C gene polymorphism in coding regions may have a higher risk of developing asthma. ..
  89. Miyoshi K, Obata K, Kondo T, Okamura H, Noguchi K. Interleukin-18-mediated microglia/astrocyte interaction in the spinal cord enhances neuropathic pain processing after nerve injury. J Neurosci. 2008;28:12775-87 pubmed publisher
    ..Thus, blocking IL-18 signaling in glial cells might provide a fruitful strategy for treating neuropathic pain. ..
  90. Walberer M, Rueger M, Simard M, Emig B, Jander S, Fink G, et al. Dynamics of neuroinflammation in the macrosphere model of arterio-arterial embolic focal ischemia: an approximation to human stroke patterns. Exp Transl Stroke Med. 2010;2:22 pubmed publisher
    ..We therefore suggest that the macrosphere model is highly appropriate for studying the pathophysiology of stroke in a translational approach from rodent to human. ..