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

Top Publications

  1. Nagarajan N, Kronenberg M. Invariant NKT cells amplify the innate immune response to lipopolysaccharide. J Immunol. 2007;178:2706-13 pubmed
  2. Netea M, Joosten L, Lewis E, Jensen D, Voshol P, Kullberg B, et al. Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistance. Nat Med. 2006;12:650-6 pubmed
    ..Obesity of Il18-/- mice resulted from accumulation of fat tissue based on increased food intake...
  3. Andoniou C, van Dommelen S, Voigt V, Andrews D, Brizard G, Asselin Paturel C, et al. Interaction between conventional dendritic cells and natural killer cells is integral to the activation of effective antiviral immunity. Nat Immunol. 2005;6:1011-9 pubmed
    ..receptor and NKG2D ligand, whereas the production of interferon-gamma by NK cells relied mainly on DC-derived interleukin 18. Although Toll-like receptor 9 contributes to antiviral immunity, we found that signaling pathways independent ..
  4. Weiss D, Takeda K, Akira S, Zychlinsky A, Moreno E. MyD88, but not toll-like receptors 4 and 2, is required for efficient clearance of Brucella abortus. Infect Immun. 2005;73:5137-43 pubmed
  5. Kitching A, Turner A, Wilson G, Semple T, Odobasic D, Timoshanko J, et al. IL-12p40 and IL-18 in crescentic glomerulonephritis: IL-12p40 is the key Th1-defining cytokine chain, whereas IL-18 promotes local inflammation and leukocyte recruitment. J Am Soc Nephrol. 2005;16:2023-33 pubmed
    ..These studies demonstrate that in severe experimental crescentic GN, IL-12p40 is the key Th1-defining cytokine chain, whereas IL-18 has local proinflammatory roles. ..
  6. Park C, Morel J, Amin M, Connors M, Harlow L, Koch A. Evidence of IL-18 as a novel angiogenic mediator. J Immunol. 2001;167:1644-53 pubmed
    ..05). These findings support a novel function for IL-18 as an angiogenic factor in RA and may elucidate a potential therapeutic target for angiogenesis-directed diseases. ..
  7. Kang M, Choi J, Kim B, Lee C, Cho W, Choe G, et al. IL-18 induces emphysema and airway and vascular remodeling via IFN-?, IL-17A, and IL-13. Am J Respir Crit Care Med. 2012;185:1205-17 pubmed publisher
  8. Hoshino T, Kato S, Oka N, Imaoka H, Kinoshita T, Takei S, et al. Pulmonary inflammation and emphysema: role of the cytokines IL-18 and IL-13. Am J Respir Crit Care Med. 2007;176:49-62 pubmed
    ..Our results indicate that IL-18 and IL-13 may have an important role in the pathogenesis of COPD. ..
  9. Salcedo R, Worschech A, Cardone M, Jones Y, Gyulai Z, Dai R, et al. MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18. J Exp Med. 2010;207:1625-36 pubmed publisher
    ..However, upon AOM/DSS treatment Il18(-/-) and Il18r1(-/-) mice were more susceptible to colitis and polyp formation than wild-type mice, suggesting that ..

More Information


  1. Reddy P, Teshima T, KuKuruga M, Ordemann R, Liu C, Lowler K, et al. Interleukin-18 regulates acute graft-versus-host disease by enhancing Fas-mediated donor T cell apoptosis. J Exp Med. 2001;194:1433-40 pubmed
    ..Together, these results demonstrate that IL-18 regulates acute GVHD by inducing enhanced Fas-mediated apoptosis of donor T cells early after BMT, and donor IFN-gamma is critical for this protective effect. ..
  2. Kang M, Homer R, Gallo A, Lee C, Crothers K, Cho S, et al. IL-18 is induced and IL-18 receptor alpha plays a critical role in the pathogenesis of cigarette smoke-induced pulmonary emphysema and inflammation. J Immunol. 2007;178:1948-59 pubmed
    ..They also demonstrate, in a murine modeling system, that IL-18R signaling plays a critical role in the pathogenesis of CS-induced inflammation and emphysema. ..
  3. Wei X, Leung B, Arthur H, McInnes I, Liew F. Reduced incidence and severity of collagen-induced arthritis in mice lacking IL-18. J Immunol. 2001;166:517-21 pubmed
    ..These data directly demonstrate a pivotal role of IL-18 in the development of inflammatory arthritis and suggest that antagonists to IL-18 may have therapeutic potential in rheumatic diseases. ..
  4. Melnikov V, Faubel S, Siegmund B, Lucia M, Ljubanovic D, Edelstein C. Neutrophil-independent mechanisms of caspase-1- and IL-18-mediated ischemic acute tubular necrosis in mice. J Clin Invest. 2002;110:1083-91 pubmed
    ..These results suggest a novel neutrophil-independent mechanism of IL-18-mediated ischemic ARF. ..
  5. 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. ..
  6. Takagi H, Kanai T, Okazawa A, Kishi Y, Sato T, Takaishi H, et al. Contrasting action of IL-12 and IL-18 in the development of dextran sodium sulphate colitis in mice. Scand J Gastroenterol. 2003;38:837-44 pubmed
    ..These results suggest that IL-18 might function with manners different from IL-12 at some pathological conditions in the development of colitis. ..
  7. Canetti C, Leung B, Culshaw S, McInnes I, Cunha F, Liew F, et al. IL-18 enhances collagen-induced arthritis by recruiting neutrophils via TNF-alpha and leukotriene B4. J Immunol. 2003;171:1009-15 pubmed
    ..Together, these findings provide a novel mechanism whereby IL-18 can promote inflammatory diseases. ..
  8. He Z, Dursun B, Oh D, Lu L, Faubel S, Edelstein C. Macrophages are not the source of injurious interleukin-18 in ischemic acute kidney injury in mice. Am J Physiol Renal Physiol. 2009;296:F535-42 pubmed publisher
    ..In conclusion, IL-18 from adoptive transfer of macrophages is not sufficient to cause ischemic AKI. ..
  9. Van Der Sluijs K, Van Elden L, Arens R, Nijhuis M, Schuurman R, Florquin S, et al. Enhanced viral clearance in interleukin-18 gene-deficient mice after pulmonary infection with influenza A virus. Immunology. 2005;114:112-20 pubmed
    ..Tumour necrosis factor-alpha production by CD4(+) T cells was significantly lower in IL-18(-/-) mice than in wildtype mice. Our data indicate that endogenous IL-18 impairs viral clearance during influenza A infection. ..
  10. Chaix J, Tessmer M, Hoebe K, Fuseri N, Ryffel B, Dalod M, et al. Cutting edge: Priming of NK cells by IL-18. J Immunol. 2008;181:1627-31 pubmed
    ..This suggests that priming by IL-18 leads to an improved translation of IFN-gamma mRNA. These results reveal a novel type of cooperation between IL-12 and IL-18 that requires the sequential action of these cytokines. ..
  11. Wild J, Sigounas A, Sur N, Siddiqui M, Alam R, Kurimoto M, et al. IFN-gamma-inducing factor (IL-18) increases allergic sensitization, serum IgE, Th2 cytokines, and airway eosinophilia in a mouse model of allergic asthma. J Immunol. 2000;164:2701-10 pubmed
    ..This is the first report demonstrating that IL-18 promotes a Th2 phenotype in vivo, and potently induces allergic sensitization. These results suggest that IL-18 may contribute to the pathogenesis of allergic asthma. ..
  12. Helmby H, Grencis R. IL-18 regulates intestinal mastocytosis and Th2 cytokine production independently of IFN-gamma during Trichinella spiralis infection. J Immunol. 2002;169:2553-60 pubmed
    ..Hence, IL-18 plays a significant biological role as a negative regulator of intestinal mast cell responses and may promote the survival of intestinal parasites in vivo. ..
  13. Cumberbatch M, Dearman R, Antonopoulos C, Groves R, Kimber I. Interleukin (IL)-18 induces Langerhans cell migration by a tumour necrosis factor-alpha- and IL-1beta-dependent mechanism. Immunology. 2001;102:323-30 pubmed
    ..Importantly, not only was IL-18 able to contribute to the regulation of LC migration, it was found to be essential for the manifestation of these processes in response to topical sensitization with the contact allergen oxazolone. ..
  14. Elinav E, Strowig T, Kau A, Henao Mejia J, Thaiss C, Booth C, et al. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell. 2011;145:745-57 pubmed publisher
    ..Altogether, perturbations in this inflammasome pathway, including NLRP6, ASC, caspase-1, and IL-18, may constitute a predisposing or initiating event in some cases of human IBD. ..
  15. Pien G, Satoskar A, Takeda K, Akira S, Biron C. Cutting edge: selective IL-18 requirements for induction of compartmental IFN-gamma responses during viral infection. J Immunol. 2000;165:4787-91 pubmed
    ..Taken together, our results delineate contrasting compartmental requirements for IL-18 and suggest that preservation of local, hepatic IFN-gamma production is critical for host defense during murine cytomegalovirus challenge. ..
  16. Freudenberg M, Merlin T, Kalis C, Chvatchko Y, Stübig H, Galanos C. Cutting edge: a murine, IL-12-independent pathway of IFN-gamma induction by gram-negative bacteria based on STAT4 activation by Type I IFN and IL-18 signaling. J Immunol. 2002;169:1665-8 pubmed
    ..This pathway participates in the induction of IFN-gamma by Gram-negative bacteria and is therefore expected to play a role whenever IFN-alpha or IFN-beta and IL-18 are produced concomitantly during bacterial, viral, or other infections. ..
  17. Kupz A, Guarda G, Gebhardt T, Sander L, Short K, Diavatopoulos D, et al. NLRC4 inflammasomes in dendritic cells regulate noncognate effector function by memory CD8? T cells. Nat Immunol. 2012;13:162-9 pubmed publisher
    ..Although this activation released interleukin 18 (IL-18) and IL-1?, only IL-18 was required for IFN-? production by memory CD8(+) T cells...
  18. 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. ..
  19. Terada M, Tsutsui H, Imai Y, Yasuda K, Mizutani H, Yamanishi K, et al. Contribution of IL-18 to atopic-dermatitis-like skin inflammation induced by Staphylococcus aureus product in mice. Proc Natl Acad Sci U S A. 2006;103:8816-21 pubmed
    ..b>il18-/-BALB/c mice similarly evaded SDS/SpA-induced AD...
  20. Adachi K, Tsutsui H, Kashiwamura S, Seki E, Nakano H, Takeuchi O, et al. Plasmodium berghei infection in mice induces liver injury by an IL-12- and toll-like receptor/myeloid differentiation factor 88-dependent mechanism. J Immunol. 2001;167:5928-34 pubmed
    ..berghei infection of mice induces activation of the TLR-MyD88 signaling pathway which results in IL-12 production and activation of the perforin-dependent cytotoxic activities of MHC-unrestricted hepatic lymphocytes. ..
  21. Sugimoto T, Ishikawa Y, Yoshimoto T, Hayashi N, Fujimoto J, Nakanishi K. Interleukin 18 acts on memory T helper cells type 1 to induce airway inflammation and hyperresponsiveness in a naive host mouse. J Exp Med. 2004;199:535-45 pubmed
    ..Thus, Ag and IL-18 stimulate memory Th1 cells to induce severe airway inflammation and AHR in the naive host. ..
  22. Iwai Y, Hemmi H, Mizenina O, Kuroda S, Suda K, Steinman R. An IFN-gamma-IL-18 signaling loop accelerates memory CD8+ T cell proliferation. PLoS ONE. 2008;3:e2404 pubmed publisher
    ..These results indicate that a positive regulatory loop involving IFN-gamma and IL-18 signaling contributes to the accelerated memory CD8(+) T cell proliferation during a recall response to antigen presented by DCs. ..
  23. Swann J, Vesely M, Silva A, Sharkey J, Akira S, Schreiber R, et al. Demonstration of inflammation-induced cancer and cancer immunoediting during primary tumorigenesis. Proc Natl Acad Sci U S A. 2008;105:652-6 pubmed publisher
    ..Overall, these data not only confirm the key role that MyD88 plays in promoting tumor development but also demonstrate that inflammation-induced carcinogenesis and cancer immunoediting can indeed occur in the same mouse tumor model. ..
  24. Wei X, Leung B, Niedbala W, Piedrafita D, Feng G, Sweet M, et al. Altered immune responses and susceptibility to Leishmania major and Staphylococcus aureus infection in IL-18-deficient mice. J Immunol. 1999;163:2821-8 pubmed
  25. Schultz M, Knapp S, Florquin S, Pater J, Takeda K, Akira S, et al. Interleukin-18 impairs the pulmonary host response to Pseudomonas aeruginosa. Infect Immun. 2003;71:1630-4 pubmed
    ..These results demonstrate that the presence of endogenous IL-18 activity facilitates inflammatory responses in the lung during Pseudomonas pneumonia, concurrently impairing bacterial clearance. ..
  26. Takeda K, Cretney E, Hayakawa Y, Ota T, Akiba H, Ogasawara K, et al. TRAIL identifies immature natural killer cells in newborn mice and adult mouse liver. Blood. 2005;105:2082-9 pubmed
    ..This study is the first to describe the concomitant maturation of NK cell effector function with surface phenotype in vivo and implies an important defense role for NK cell TRAIL in the developing immune system. ..
  27. 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...
  28. Antonopoulos C, Cumberbatch M, Mee J, Dearman R, Wei X, Liew F, et al. IL-18 is a key proximal mediator of contact hypersensitivity and allergen-induced Langerhans cell migration in murine epidermis. J Leukoc Biol. 2008;83:361-7 pubmed
    ..These data indicate that IL-18 is a key proximal mediator of LC migration and CHS, acting upstream of IL-1 beta and TNF-alpha, and may play a central role in regulation of cutaneous immune responses. ..
  29. Haring J, Harty J. Interleukin-18-related genes are induced during the contraction phase but do not play major roles in regulating the dynamics or function of the T-cell response to Listeria monocytogenes infection. Infect Immun. 2009;77:1894-903 pubmed publisher
    ..monocytogenes infection. ..
  30. Sugawara I, Yamada H, Kaneko H, Mizuno S, Takeda K, Akira S. Role of interleukin-18 (IL-18) in mycobacterial infection in IL-18-gene-disrupted mice. Infect Immun. 1999;67:2585-9 pubmed
    ..Therefore, IL-18 is important for the generation of protective immunity to mycobacteria, and its main function is the induction of IFN-gamma expression. ..
  31. Tsutsui H, Kayagaki N, Kuida K, Nakano H, Hayashi N, Takeda K, et al. Caspase-1-independent, Fas/Fas ligand-mediated IL-18 secretion from macrophages causes acute liver injury in mice. Immunity. 1999;11:359-67 pubmed
    ..These results indicate a caspase-1-independent pathway of IL-18 secretion from FasL-stimulated macrophages and its critical involvement in FasL-induced liver injury. ..
  32. 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. ..
  33. Seki E, Tsutsui H, Tsuji N, Hayashi N, Adachi K, Nakano H, et al. Critical roles of myeloid differentiation factor 88-dependent proinflammatory cytokine release in early phase clearance of Listeria monocytogenes in mice. J Immunol. 2002;169:3863-8 pubmed
    ..These results indicated a critical role for TLRs/MyD88-dependent IL-12/TNF-alpha production and for IL-12- and IL-18-mediated IFN-gamma production in early phase clearance of LM. ..
  34. Lauw F, Branger J, Florquin S, Speelman P, van Deventer S, Akira S, et al. IL-18 improves the early antimicrobial host response to pneumococcal pneumonia. J Immunol. 2002;168:372-8 pubmed
    ..These data suggest that endogenous IL-18, but not IL-12, plays an important role in the early antibacterial host response during pneumococcal pneumonia. ..
  35. Morel J, Park C, Woods J, Koch A. A novel role for interleukin-18 in adhesion molecule induction through NF kappa B and phosphatidylinositol (PI) 3-kinase-dependent signal transduction pathways. J Biol Chem. 2001;276:37069-75 pubmed
    ..IL-18 requires NF kappa B as well as PI 3-kinase to induce VCAM-1 on RA synovial fibroblasts, suggesting that there may be two distinct pathways in IL-18-induced adhesion molecule expression. ..
  36. Adachi O, Kawai T, Takeda K, Matsumoto M, Tsutsui H, Sakagami M, et al. Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function. Immunity. 1998;9:143-50 pubmed
    ..Taken together, these results demonstrate that MyD88 is a critical component in the signaling cascade that is mediated by IL-1 receptor as well as IL-18 receptor. ..
  37. Tenger C, Sundborger A, Jawien J, Zhou X. IL-18 accelerates atherosclerosis accompanied by elevation of IFN-gamma and CXCL16 expression independently of T cells. Arterioscler Thromb Vasc Biol. 2005;25:791-6 pubmed
    ..The current data suggest that the proatherogenic effect of IL-18 can occur in the absence of T cells and that IFN-gamma secreted by macrophages, NK cells, and vascular cells is sufficient for the disease progression. ..
  38. Hashimoto W, Osaki T, Okamura H, Robbins P, Kurimoto M, Nagata S, et al. Differential antitumor effects of administration of recombinant IL-18 or recombinant IL-12 are mediated primarily by Fas-Fas ligand- and perforin-induced tumor apoptosis, respectively. J Immunol. 1999;163:583-9 pubmed
    ..We conclude that the antitumor effect of IL-18 is exerted predominantly through a Fas-dependent pathway. The perforin pathway, however, appears to be the predominant cytolytic pathway mediating IL-12 antitumor effects. ..
  39. Hoshino T, Okamoto M, Sakazaki Y, Kato S, Young H, Aizawa H. Role of proinflammatory cytokines IL-18 and IL-1beta in bleomycin-induced lung injury in humans and mice. Am J Respir Cell Mol Biol. 2009;41:661-70 pubmed publisher
    ..Thus, our results provide evidence for an important role of IL-1beta and IL-18 in chemotherapy-induced lung injury. ..
  40. Zhang H, Hile K, Asanuma H, VanderBrink B, Franke E, Campbell M, et al. IL-18 mediates proapoptotic signaling in renal tubular cells through a Fas ligand-dependent mechanism. Am J Physiol Renal Physiol. 2011;301:F171-8 pubmed publisher
    ..This study reveals that IL-18 is a significant mediator of obstruction-induced tubular cell apoptosis, and it demonstrates that IL-18 stimulates proapoptotic signaling through a FasL-dependent mechanism. ..
  41. Miao E, Leaf I, Treuting P, Mao D, Dors M, Sarkar A, et al. Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria. Nat Immunol. 2010;11:1136-42 pubmed publisher
    ..This demonstrates that activation of caspase-1 clears intracellular bacteria in vivo independently of IL-1? and IL-18 and establishes pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system...
  42. Tominaga K, Yoshimoto T, Torigoe K, Kurimoto M, Matsui K, Hada T, et al. IL-12 synergizes with IL-18 or IL-1beta for IFN-gamma production from human T cells. Int Immunol. 2000;12:151-60 pubmed
    ..We also show that T(h)1 cells but not T(h)2 cells have increased expression of IL-18R and IL-1R, and produce IFN-gamma in response to IL-18 and/or IL-1beta. ..
  43. Elhage R, Jawien J, Rudling M, Ljunggren H, Takeda K, Akira S, et al. Reduced atherosclerosis in interleukin-18 deficient apolipoprotein E-knockout mice. Cardiovasc Res. 2003;59:234-40 pubmed
    ..These data show reduced atherosclerosis and Th1 activity in spite of increased serum cholesterol in IL-18 deficient apoE(-/-) mice. They support a proatherogenic role for IL-18. ..
  44. Okamoto M, Kato S, Oizumi K, Kinoshita M, Inoue Y, Hoshino K, et al. Interleukin 18 (IL-18) in synergy with IL-2 induces lethal lung injury in mice: a potential role for cytokines, chemokines, and natural killer cells in the pathogenesis of interstitial pneumonia. Blood. 2002;99:1289-98 pubmed
    b>Interleukin 18 (IL-18) was discovered as an interferon-gamma (IFN-gamma)-inducing factor and plays important roles in natural killer (NK) cell activation...
  45. Spörri R, Joller N, Hilbi H, Oxenius A. A novel role for neutrophils as critical activators of NK cells. J Immunol. 2008;181:7121-30 pubmed
    ..We propose a novel central role for neutrophils as essential IL-18 producers and hence NK cell "helpers" in bacterial infection. ..
  46. 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. ..
  47. Akira S. The role of IL-18 in innate immunity. Curr Opin Immunol. 2000;12:59-63 pubmed
    ..The IL-18 receptor system and its signal transduction pathway are analogous to those of the IL-1 receptor. Mice deficient in IL-18 have demonstrated its critical role in natural killer cell activity and in vivo Th1 response. ..
  48. Mayer Barber K, Barber D, Shenderov K, White S, Wilson M, Cheever A, et al. Caspase-1 independent IL-1beta production is critical for host resistance to mycobacterium tuberculosis and does not require TLR signaling in vivo. J Immunol. 2010;184:3326-30 pubmed publisher
    ..Together our findings reveal a major role for IL-1beta in host resistance to M. tuberculosis and indicate that during this infection the cytokine can be generated by a mechanism that does not require TLR signaling or caspase-1. ..
  49. Konishi H, Tsutsui H, Murakami T, Yumikura Futatsugi S, Yamanaka K, Tanaka M, et al. IL-18 contributes to the spontaneous development of atopic dermatitis-like inflammatory skin lesion independently of IgE/stat6 under specific pathogen-free conditions. Proc Natl Acad Sci U S A. 2002;99:11340-5 pubmed
    ..Our present study might provide insight into understanding the pathogenesis of and establishing therapeutics for chronic inflammatory skin diseases including AD. ..
  50. Tyznik A, Tupin E, Nagarajan N, Her M, Benedict C, Kronenberg M. Cutting edge: the mechanism of invariant NKT cell responses to viral danger signals. J Immunol. 2008;181:4452-6 pubmed
    ..Consequently, iNKT cells have the ability to respond to a variety of microbes, including viruses, in an Ag-independent manner, suggesting they may play a broad role in antipathogen defenses despite their limited TCR repertoire. ..
  51. Wang Y, Chaudhri G, Jackson R, Karupiah G. IL-12p40 and IL-18 play pivotal roles in orchestrating the cell-mediated immune response to a poxvirus infection. J Immunol. 2009;183:3324-31 pubmed publisher
    ..Taken together, our data indicate that IL-12p40 and IL-18 act in concert and play an important antiviral role through the up-regulation of IFN-gamma production and cell-mediated immune responses...
  52. Raupach B, Peuschel S, Monack D, Zychlinsky A. Caspase-1-mediated activation of interleukin-1beta (IL-1beta) and IL-18 contributes to innate immune defenses against Salmonella enterica serovar Typhimurium infection. Infect Immun. 2006;74:4922-6 pubmed
    ..Thus, we show that Casp-1 is essential for host innate immune defense against S. enterica serovar Typhimurium and that Casp-1 substrates are required at distinct times and anatomical sites. ..
  53. Zeiser R, Zambricki E, Leveson Gower D, Kambham N, Beilhack A, Negrin R. Host-derived interleukin-18 differentially impacts regulatory and conventional T cell expansion during acute graft-versus-host disease. Biol Blood Marrow Transplant. 2007;13:1427-38 pubmed
    ..We conclude that host-derived IL-18 is a major factor for IFN-gamma production that may have a protective effect on CD4(+)-mediated aGVHD, but is nonessential for Treg expansion in an allogeneic environment. ..
  54. Morel J, Park C, Kumar P, Koch A. Interleukin-18 induces rheumatoid arthritis synovial fibroblast CXC chemokine production through NFkappaB activation. Lab Invest. 2001;81:1371-83 pubmed
    ..These results indicate a novel role for IL-18 in inducing RA synovial fibroblast expression of CXC chemokines through NFkappaB and place this cytokine in a strategic role in the local inflammation observed in RA. ..
  55. Joosten L, van de Loo F, Lubberts E, Helsen M, Netea M, van der Meer J, et al. An IFN-gamma-independent proinflammatory role of IL-18 in murine streptococcal cell wall arthritis. J Immunol. 2000;165:6553-8 pubmed
    ..The present study indicates that IL-18 is a proinflammatory cytokine during the onset of murine SCW arthritis, and this inflammatory role of IL-18 is IFN-gamma independent. ..
  56. Bani Hani A, Leslie J, Asanuma H, Dinarello C, Campbell M, Meldrum D, et al. IL-18 neutralization ameliorates obstruction-induced epithelial-mesenchymal transition and renal fibrosis. Kidney Int. 2009;76:500-11 pubmed publisher
    ..Our study demonstrates that IL-18 is a significant mediator of obstruction-induced renal fibrosis and epithelial- mesenchymal transition independent of downstream TGF-beta1 or TNF-alpha production. ..
  57. Kohno K, Kurimoto M. Interleukin 18, a cytokine which resembles IL-1 structurally and IL-12 functionally but exerts its effect independently of both. Clin Immunol Immunopathol. 1998;86:11-5 pubmed
  58. Li H, Willingham S, Ting J, Re F. Cutting edge: inflammasome activation by alum and alum's adjuvant effect are mediated by NLRP3. J Immunol. 2008;181:17-21 pubmed
  59. Schneider B, Korbel D, Hagens K, Koch M, Raupach B, Enders J, et al. A role for IL-18 in protective immunity against Mycobacterium tuberculosis. Eur J Immunol. 2010;40:396-405 pubmed publisher
    ..Thus, IL-18 plays a decisive role in protective immunity against tuberculosis. ..
  60. Wiersinga W, Wieland C, van der Windt G, de Boer A, Florquin S, Dondorp A, et al. Endogenous interleukin-18 improves the early antimicrobial host response in severe melioidosis. Infect Immun. 2007;75:3739-46 pubmed
    ..Together, these data indicate that the enhanced production of IL-18 in melioidosis is an essential part of a protective immune response to this severe infection. ..
  61. Kastenmüller W, Torabi Parizi P, Subramanian N, Lämmermann T, Germain R. A spatially-organized multicellular innate immune response in lymph nodes limits systemic pathogen spread. Cell. 2012;150:1235-48 pubmed publisher
  62. Kawakami K, Kinjo Y, Yara S, Uezu K, Koguchi Y, Tohyama M, et al. Enhanced gamma interferon production through activation of Valpha14(+) natural killer T cells by alpha-galactosylceramide in interleukin-18-deficient mice with systemic cryptococcosis. Infect Immun. 2001;69:6643-50 pubmed
    ..Our results indicated that in IL-18KO mice, IFN-gamma synthesis was enhanced through overproduction of IL-12 and IL-4 after intravenous infection with C. neoformans and a ligand-specific activation of Valpha14(+) NKT cells. ..