Il6

Summary

Gene Symbol: Il6
Description: interleukin 6
Alias: Il-6, interleukin-6, B-cell hybridoma growth factor, interleukin HP-1
Species: mouse
Products:     Il6

Top Publications

  1. Gomez C, Nomellini V, Baila H, Oshima K, Kovacs E. Comparison of the effects of aging and IL-6 on the hepatic inflammatory response in two models of systemic injury: scald injury versus i.p. LPS administration. Shock. 2009;31:178-84 pubmed publisher
    ..Our results suggest that the nature of the insult will determine the degree of remote injury in aged animals. In addition, the role of IL-6 as a contributing factor of tissue injury may be insult specific. ..
  2. Sonderegger I, Kisielow J, Meier R, King C, Kopf M. IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo. Eur J Immunol. 2008;38:1833-8 pubmed publisher
    ..IL-6 induced Th17 differentiation independent of and much more potently than IL-21 in vitro. These data suggest that IL-6 is sufficient to drive Th17 development and associated autoimmunity in vivo in the absence of IL-21 or IL-21R...
  3. Quinton L, Jones M, Robson B, Simms B, Whitsett J, Mizgerd J. Alveolar epithelial STAT3, IL-6 family cytokines, and host defense during Escherichia coli pneumonia. Am J Respir Cell Mol Biol. 2008;38:699-706 pubmed publisher
    ..Together, these results indicate that during E. coli pneumonia, select IL-6 family members activate alveolar epithelial STAT3, which functions to promote neutrophil recruitment and to limit both infection and lung injury. ..
  4. Matsumoto S, Hara T, Mitsuyama K, Yamamoto M, Tsuruta O, Sata M, et al. Essential roles of IL-6 trans-signaling in colonic epithelial cells, induced by the IL-6/soluble-IL-6 receptor derived from lamina propria macrophages, on the development of colitis-associated premalignant cancer in a murine model. J Immunol. 2010;184:1543-51 pubmed publisher
    ..Treatment with soluble gp130Fc significantly reduced the CApC. IL-6 trans-signaling in epithelial cells induced by macrophage-derived IL-6/sIL-6R alpha plays a crucial role in the development of CAC. ..
  5. Fosgerau K, Galle P, Hansen T, Albrechtsen A, Rieper C, Pedersen B, et al. Interleukin-6 autoantibodies are involved in the pathogenesis of a subset of type 2 diabetes. J Endocrinol. 2010;204:265-73 pubmed publisher
    Interleukin-6 (IL6) is critically involved in inflammation and metabolism. About 1% of people produce IL6 autoantibodies (aAb-IL6) that impair IL6 signaling in vivo...
  6. He G, Dhar D, Nakagawa H, Font Burgada J, Ogata H, Jiang Y, et al. Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling. Cell. 2013;155:384-96 pubmed publisher
    ..This may be a general mechanism that drives other IL-6-producing malignancies. ..
  7. Zheng Y, Humphry M, Maguire J, Bennett M, Clarke M. Intracellular interleukin-1 receptor 2 binding prevents cleavage and activity of interleukin-1?, controlling necrosis-induced sterile inflammation. Immunity. 2013;38:285-95 pubmed publisher
    ..Thus, we report a cell type-dependent process that fundamentally governs IL-1? activity postnecrosis and the mechanism allowing conditional release of this blockade. ..
  8. Vida M, Serrano A, Romero Cuevas M, Pavón F, Gonzalez Rodriguez A, Gavito A, et al. IL-6 cooperates with peroxisome proliferator-activated receptor-?-ligands to induce liver fatty acid binding protein (LFABP) up-regulation. Liver Int. 2013;33:1019-28 pubmed publisher
    ..These effects may have important implications in the postprandial increase in FA uptake and intracellular trafficking in the liver. ..
  9. Putoczki T, Thiem S, Loving A, Busuttil R, Wilson N, Ziegler P, et al. Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically. Cancer Cell. 2013;24:257-71 pubmed publisher
    ..Our results identify IL-11 signaling as a potential therapeutic target for the treatment of gastrointestinal cancers. ..
  10. Bonetto A, Aydogdu T, Jin X, Zhang Z, Zhan R, Puzis L, et al. JAK/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia. Am J Physiol Endocrinol Metab. 2012;303:E410-21 pubmed publisher
    ..Thus STAT3 could represent a novel therapeutic target for the preservation of skeletal muscle in cachexia...

Detail Information

Publications101 found, 100 shown here

  1. Gomez C, Nomellini V, Baila H, Oshima K, Kovacs E. Comparison of the effects of aging and IL-6 on the hepatic inflammatory response in two models of systemic injury: scald injury versus i.p. LPS administration. Shock. 2009;31:178-84 pubmed publisher
    ..Our results suggest that the nature of the insult will determine the degree of remote injury in aged animals. In addition, the role of IL-6 as a contributing factor of tissue injury may be insult specific. ..
  2. Sonderegger I, Kisielow J, Meier R, King C, Kopf M. IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo. Eur J Immunol. 2008;38:1833-8 pubmed publisher
    ..IL-6 induced Th17 differentiation independent of and much more potently than IL-21 in vitro. These data suggest that IL-6 is sufficient to drive Th17 development and associated autoimmunity in vivo in the absence of IL-21 or IL-21R...
  3. Quinton L, Jones M, Robson B, Simms B, Whitsett J, Mizgerd J. Alveolar epithelial STAT3, IL-6 family cytokines, and host defense during Escherichia coli pneumonia. Am J Respir Cell Mol Biol. 2008;38:699-706 pubmed publisher
    ..Together, these results indicate that during E. coli pneumonia, select IL-6 family members activate alveolar epithelial STAT3, which functions to promote neutrophil recruitment and to limit both infection and lung injury. ..
  4. Matsumoto S, Hara T, Mitsuyama K, Yamamoto M, Tsuruta O, Sata M, et al. Essential roles of IL-6 trans-signaling in colonic epithelial cells, induced by the IL-6/soluble-IL-6 receptor derived from lamina propria macrophages, on the development of colitis-associated premalignant cancer in a murine model. J Immunol. 2010;184:1543-51 pubmed publisher
    ..Treatment with soluble gp130Fc significantly reduced the CApC. IL-6 trans-signaling in epithelial cells induced by macrophage-derived IL-6/sIL-6R alpha plays a crucial role in the development of CAC. ..
  5. Fosgerau K, Galle P, Hansen T, Albrechtsen A, Rieper C, Pedersen B, et al. Interleukin-6 autoantibodies are involved in the pathogenesis of a subset of type 2 diabetes. J Endocrinol. 2010;204:265-73 pubmed publisher
    Interleukin-6 (IL6) is critically involved in inflammation and metabolism. About 1% of people produce IL6 autoantibodies (aAb-IL6) that impair IL6 signaling in vivo...
  6. He G, Dhar D, Nakagawa H, Font Burgada J, Ogata H, Jiang Y, et al. Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling. Cell. 2013;155:384-96 pubmed publisher
    ..This may be a general mechanism that drives other IL-6-producing malignancies. ..
  7. Zheng Y, Humphry M, Maguire J, Bennett M, Clarke M. Intracellular interleukin-1 receptor 2 binding prevents cleavage and activity of interleukin-1?, controlling necrosis-induced sterile inflammation. Immunity. 2013;38:285-95 pubmed publisher
    ..Thus, we report a cell type-dependent process that fundamentally governs IL-1? activity postnecrosis and the mechanism allowing conditional release of this blockade. ..
  8. Vida M, Serrano A, Romero Cuevas M, Pavón F, Gonzalez Rodriguez A, Gavito A, et al. IL-6 cooperates with peroxisome proliferator-activated receptor-?-ligands to induce liver fatty acid binding protein (LFABP) up-regulation. Liver Int. 2013;33:1019-28 pubmed publisher
    ..These effects may have important implications in the postprandial increase in FA uptake and intracellular trafficking in the liver. ..
  9. Putoczki T, Thiem S, Loving A, Busuttil R, Wilson N, Ziegler P, et al. Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically. Cancer Cell. 2013;24:257-71 pubmed publisher
    ..Our results identify IL-11 signaling as a potential therapeutic target for the treatment of gastrointestinal cancers. ..
  10. Bonetto A, Aydogdu T, Jin X, Zhang Z, Zhan R, Puzis L, et al. JAK/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia. Am J Physiol Endocrinol Metab. 2012;303:E410-21 pubmed publisher
    ..Thus STAT3 could represent a novel therapeutic target for the preservation of skeletal muscle in cachexia...
  11. Zheng Y, Valdez P, Danilenko D, Hu Y, Sa S, Gong Q, et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med. 2008;14:282-9 pubmed publisher
    ..rodentium infection. Together, our data identify a new innate immune function for IL-22 in regulating early defense mechanisms against A/E bacterial pathogens...
  12. Wang L, Yi T, Kortylewski M, Pardoll D, Zeng D, Yu H. IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med. 2009;206:1457-64 pubmed publisher
    ..The Th17 response can thus promote tumor growth, in part via an IL-6-Stat3 pathway. ..
  13. Hilbert D, Kopf M, Mock B, Kohler G, Rudikoff S. Interleukin 6 is essential for in vivo development of B lineage neoplasms. J Exp Med. 1995;182:243-8 pubmed
    ..These studies define the essential role of IL-6 in the development of B lineage tumors in vivo and provide experimental support for continued efforts to modulate this cytokine in the treatment of appropriate human B cell malignancies. ..
  14. Fantuzzi G, Dinarello C. The inflammatory response in interleukin-1 beta-deficient mice: comparison with other cytokine-related knock-out mice. J Leukoc Biol. 1996;59:489-93 pubmed
  15. Ernst M, Najdovska M, Grail D, Lundgren May T, Buchert M, Tye H, et al. STAT3 and STAT1 mediate IL-11-dependent and inflammation-associated gastric tumorigenesis in gp130 receptor mutant mice. J Clin Invest. 2008;118:1727-38 pubmed publisher
    ..Collectively, our data have identified IL-11 as a crucial cytokine promoting chronic gastric inflammation and associated tumorigenesis mediated by excessive activation of STAT3 and STAT1. ..
  16. Clarke M, Talib S, Figg N, Bennett M. Vascular smooth muscle cell apoptosis induces interleukin-1-directed inflammation: effects of hyperlipidemia-mediated inhibition of phagocytosis. Circ Res. 2010;106:363-72 pubmed publisher
    ..Thus, failed clearance of apoptotic VSMCs caused by hyperlipidemia in vivo may promote the increased serum cytokines and chronic inflammation associated with atherosclerosis. ..
  17. Passos S, Silver J, O Hara A, Sehy D, Stumhofer J, Hunter C. IL-6 promotes NK cell production of IL-17 during toxoplasmosis. J Immunol. 2010;184:1776-83 pubmed publisher
  18. Neveu W, Bernardo E, Allard J, Nagaleekar V, Wargo M, Davis R, et al. Fungal allergen ?-glucans trigger p38 mitogen-activated protein kinase-mediated IL-6 translation in lung epithelial cells. Am J Respir Cell Mol Biol. 2011;45:1133-41 pubmed publisher
    ..Thus, ?-glucans may constitute a common determinant of the fungal and plant-derived allergens responsible for some of the pathological features in allergic asthma. ..
  19. Quintana A, Erta M, Ferrer B, Comes G, Giralt M, Hidalgo J. Astrocyte-specific deficiency of interleukin-6 and its receptor reveal specific roles in survival, body weight and behavior. Brain Behav Immun. 2013;27:162-73 pubmed publisher
    ..Our results suggest important roles of the astrocyte IL-6 system on normal brain physiology, in some cases totally unexpected from previous results with total IL-6 KO mice. ..
  20. Kopf M, Herren S, Wiles M, Pepys M, Kosco Vilbois M. Interleukin 6 influences germinal center development and antibody production via a contribution of C3 complement component. J Exp Med. 1998;188:1895-906 pubmed
    ..These findings reveal that the germinal center produces and uses molecules of the innate immune system, evolutionarily pirating them in order to optimally generate high affinity antibody responses. ..
  21. Tebbutt N, Giraud A, Inglese M, Jenkins B, Waring P, Clay F, et al. Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice. Nat Med. 2002;8:1089-97 pubmed
    ..We propose a model whereby mucosal wound healing depends solely on activation of STAT1/3, whereas gastric hyperplasia ensues when the coordinated activation of the STAT1/3 and SHP2-Ras-ERK pathways is disrupted. ..
  22. Malagarie Cazenave S, Segui B, Levèque S, Garcia V, Carpentier S, Altié M, et al. Role of FAN in tumor necrosis factor-alpha and lipopolysaccharide-induced interleukin-6 secretion and lethality in D-galactosamine-sensitized mice. J Biol Chem. 2004;279:18648-55 pubmed
    ..These findings highlight the role of FAN and IL-6 in the inflammatory response initiated by endotoxin, implicating TNFalpha. ..
  23. Wong P, Egan P, Croker B, O Donnell K, Sims N, Drake S, et al. SOCS-3 negatively regulates innate and adaptive immune mechanisms in acute IL-1-dependent inflammatory arthritis. J Clin Invest. 2006;116:1571-81 pubmed
    ..These findings provide direct in vivo evidence that endogenous SOCS-3 is a critical negative regulator of multiple cell types orchestrating inflammatory joint disease. ..
  24. Salomon R, Hoffmann E, Webster R. Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection. Proc Natl Acad Sci U S A. 2007;104:12479-81 pubmed
    ..Because cytokine inhibition does not protect against death, therapies that target the virus rather than cytokines may be preferable. ..
  25. Hayashi T, Cottam H, Chan M, Jin G, Tawatao R, Crain B, et al. Mast cell-dependent anorexia and hypothermia induced by mucosal activation of Toll-like receptor 7. Am J Physiol Regul Integr Comp Physiol. 2008;295:R123-32 pubmed publisher
    ..Our results thus suggest that tissue mast cells may play a role in the anorexia induced by mucosal activation of TLR7. ..
  26. Fielding C, McLoughlin R, McLeod L, Colmont C, Najdovska M, Grail D, et al. IL-6 regulates neutrophil trafficking during acute inflammation via STAT3. J Immunol. 2008;181:2189-95 pubmed
  27. Kim S, Takahashi H, Lin W, Descargues P, Grivennikov S, Kim Y, et al. Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature. 2009;457:102-6 pubmed publisher
    ..These results explain how advanced cancer cells usurp components of the host innate immune system, including bone-marrow-derived myeloid progenitors, to generate an inflammatory microenvironment hospitable for metastatic growth...
  28. Banerjee I, Fuseler J, Intwala A, Baudino T. IL-6 loss causes ventricular dysfunction, fibrosis, reduced capillary density, and dramatically alters the cell populations of the developing and adult heart. Am J Physiol Heart Circ Physiol. 2009;296:H1694-704 pubmed publisher
    ..Taken together, these data demonstrate that a loss of IL-6 causes cardiac dysfunction by shifting the cardiac cell populations, altering the extracellular matrix, and disrupting critical cell-cell interactions. ..
  29. Matthews V, Allen T, Risis S, Chan M, Henstridge D, Watson N, et al. Interleukin-6-deficient mice develop hepatic inflammation and systemic insulin resistance. Diabetologia. 2010;53:2431-41 pubmed publisher
    ..We aimed to determine whether global deletion of Il6 in mice (Il6 (-/-)) results in standard chow-induced and high-fat diet (HFD)-induced obesity, hepatosteatosis, ..
  30. Schuett H, Oestreich R, Waetzig G, Annema W, Luchtefeld M, Hillmer A, et al. Transsignaling of interleukin-6 crucially contributes to atherosclerosis in mice. Arterioscler Thromb Vasc Biol. 2012;32:281-90 pubmed publisher
    ..These data clarify, for the first time, the critical involvement of, in particular, the transsignaling of IL-6 in CAD and warrant further investigation of sgp130Fc as a novel therapeutic for the treatment of CAD and related diseases. ..
  31. El Kasmi K, Holst J, Coffre M, Mielke L, de Pauw A, Lhocine N, et al. General nature of the STAT3-activated anti-inflammatory response. J Immunol. 2006;177:7880-8 pubmed
    ..We conclude that the AIR is a generic cytokine signaling pathway dependent on STAT3 but not unique to the IL-10R. ..
  32. Sander L, Obermeier F, Dierssen U, Kroy D, Singh A, Seidler U, et al. Gp130 signaling promotes development of acute experimental colitis by facilitating early neutrophil/macrophage recruitment and activation. J Immunol. 2008;181:3586-94 pubmed
    ..We provide evidence that IL-6 cytokines acting via gp130 are required in the acute stages of intestinal inflammation by modulating the dynamics of innate immune cell recruitment and activation. ..
  33. Bettelli E, Carrier Y, Gao W, Korn T, Strom T, Oukka M, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006;441:235-8 pubmed
    ..Our data demonstrate a dichotomy in the generation of pathogenic (T(H)17) T cells that induce autoimmunity and regulatory (Foxp3+) T cells that inhibit autoimmune tissue injury. ..
  34. Neveu W, Allard J, Dienz O, Wargo M, Ciliberto G, Whittaker L, et al. IL-6 is required for airway mucus production induced by inhaled fungal allergens. J Immunol. 2009;183:1732-8 pubmed publisher
    ..Thus, IL-6 is a key regulator of specific hallmark features of allergic airway inflammation and it could be a potential target for pulmonary diseases that are associated with goblet cell metaplasia and mucus hypersecretion. ..
  35. Maeda S, Kamata H, Luo J, Leffert H, Karin M. IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell. 2005;121:977-90 pubmed
    ..IKKbeta, therefore, orchestrates inflammatory crosstalk between hepatocytes and hematopoietic-derived cells that promotes chemical hepatocarcinogenesis. ..
  36. Shaw M, Kamada N, Kim Y, Nunez G. Microbiota-induced IL-1?, but not IL-6, is critical for the development of steady-state TH17 cells in the intestine. J Exp Med. 2012;209:251-8 pubmed publisher
    ..Thus, commensal-induced IL-1? production is a critical step for sT(H)17 differentiation in the intestine, which may have therapeutic implications for T(H)17-mediated pathologies. ..
  37. Yang Y, Ochando J, Yopp A, Bromberg J, Ding Y. IL-6 plays a unique role in initiating c-Maf expression during early stage of CD4 T cell activation. J Immunol. 2005;174:2720-9 pubmed
    ..Our findings suggest that IL-6 plays a unique role in initiating c-Maf expression after TCR engagement, and may subsequently regulate early IL-4 production and Th2 commitment. ..
  38. Penkowa M, Moos T, Carrasco J, Hadberg H, Molinero A, Bluethmann H, et al. Strongly compromised inflammatory response to brain injury in interleukin-6-deficient mice. Glia. 1999;25:343-57 pubmed
    ..Furthermore, our results suggest IL-6 is important for neuroprotection and the induction of GM-CSF and MT expression. The opposing effect of IL-6 on MT-I+II and MT-III levels in the damaged brain suggests MT isoform-specific functions. ..
  39. Wallenius V, Wallenius K, Ahren B, Rudling M, Carlsten H, Dickson S, et al. Interleukin-6-deficient mice develop mature-onset obesity. Nat Med. 2002;8:75-9 pubmed
    ..We investigated the impact of loss of IL-6 on body composition in mice lacking the gene encoding IL-6 (Il6-/- mice) and found that they developed mature-onset obesity that was partly reversed by IL-6 replacement...
  40. Wuestefeld T, Klein C, Streetz K, Betz U, Lauber J, Buer J, et al. Interleukin-6/glycoprotein 130-dependent pathways are protective during liver regeneration. J Biol Chem. 2003;278:11281-8 pubmed
    After tissue loss the liver has the unique capacity to restore its mass by hepatocyte proliferation. Interleukin-6 (IL6)-deficient mice show a lack in DNA synthesis after partial hepatectomy (PH)...
  41. Eddahri F, Denanglaire S, Bureau F, Spolski R, Leonard W, Leo O, et al. Interleukin-6/STAT3 signaling regulates the ability of naive T cells to acquire B-cell help capacities. Blood. 2009;113:2426-33 pubmed publisher
    ..Collectively, these data indicate that the ability to provide B-cell help is regulated by IL-6/IL-21 through STAT3 activation, independently of Th1, Th2, Th17, or follicular helper T cell (T(FH)) differentiation. ..
  42. Wunderlich F, Ströhle P, Könner A, Gruber S, Tovar S, Brönneke H, et al. Interleukin-6 signaling in liver-parenchymal cells suppresses hepatic inflammation and improves systemic insulin action. Cell Metab. 2010;12:237-49 pubmed publisher
    ..Thus, our results reveal an unexpected role for hepatic IL-6 signaling to limit hepatic inflammation and to protect from local and systemic insulin resistance. ..
  43. Arima Y, Harada M, Kamimura D, Park J, Kawano F, Yull F, et al. Regional neural activation defines a gateway for autoreactive T cells to cross the blood-brain barrier. Cell. 2012;148:447-57 pubmed publisher
  44. Klover P, Zimmers T, Koniaris L, Mooney R. Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice. Diabetes. 2003;52:2784-9 pubmed
    ..These data suggest that chronic IL-6 treatment selectively impairs hepatic insulin signaling in vivo, further supporting a role for IL-6 in hepatic insulin resistance of obesity. ..
  45. Nakagawa T, Tsuruoka M, Ogura H, Okuyama Y, Arima Y, Hirano T, et al. IL-6 positively regulates Foxp3+CD8+ T cells in vivo. Int Immunol. 2010;22:129-39 pubmed publisher
    ..These results suggested that Foxp3(+)CD8(+) T cells may develop in response to IL-6 under certain inflammatory conditions in vivo and may regulate some other chronic inflammation diseases. ..
  46. Booth A, Grabauskiene S, Wood S, Lu G, Burrell B, Bishop D. IL-6 promotes cardiac graft rejection mediated by CD4+ cells. J Immunol. 2011;187:5764-71 pubmed publisher
    ..In light of these findings, the utility of therapeutics targeting IL-6 should be considered for preventing cardiac allograft rejection. ..
  47. Suematsu S, Matsusaka T, Matsuda T, Ohno S, Miyazaki J, Yamamura K, et al. Generation of plasmacytomas with the chromosomal translocation t(12;15) in interleukin 6 transgenic mice. Proc Natl Acad Sci U S A. 1992;89:232-5 pubmed
    ..or mineral oil can induce plasmacytomas in BALB/c or NZB mice are not fully understood, but involvement of interleukin 6 (IL-6), a growth factor for plasmacytomas and myelomas, has been strongly suggested...
  48. Wang J, Homer R, Chen Q, Elias J. Endogenous and exogenous IL-6 inhibit aeroallergen-induced Th2 inflammation. J Immunol. 2000;165:4051-61 pubmed
    ..IL-6 may be an important anti-inflammatory, counterregulatory, and healing cytokine in the airway. ..
  49. Blindenbacher A, Wang X, Langer I, Savino R, Terracciano L, Heim M. Interleukin 6 is important for survival after partial hepatectomy in mice. Hepatology. 2003;38:674-82 pubmed
    The response to partial hepatectomy (PH) is impaired in interleukin 6 (IL-6)-deficient mice...
  50. Persson E, Voznesensky O, Huang Y, Lerner U. Increased expression of interleukin-6 by vasoactive intestinal peptide is associated with regulation of CREB, AP-1 and C/EBP, but not NF-kappaB, in mouse calvarial osteoblasts. Bone. 2005;37:513-29 pubmed
  51. Korn T, Bettelli E, Gao W, Awasthi A, Jäger A, Strom T, et al. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature. 2007;448:484-487 pubmed publisher
    ..Here we show that IL-6-deficient (Il6-/-) mice do not develop a T(H)17 response and their peripheral repertoire is dominated by Foxp3+ T(reg) cells...
  52. Suematsu S, Matsuda T, Aozasa K, Akira S, Nakano N, Ohno S, et al. IgG1 plasmacytosis in interleukin 6 transgenic mice. Proc Natl Acad Sci U S A. 1989;86:7547-51 pubmed
    b>Interleukin 6 (IL-6) has been suggested to be involved in the pathogenesis of polyclonal and monoclonal plasma cell abnormalities...
  53. Bernad A, Kopf M, Kulbacki R, Weich N, Koehler G, Gutierrez Ramos J. Interleukin-6 is required in vivo for the regulation of stem cells and committed progenitors of the hematopoietic system. Immunity. 1994;1:725-31 pubmed
  54. Kitamura K, Nakamoto Y, Kaneko S, Mukaida N. Pivotal roles of interleukin-6 in transmural inflammation in murine T cell transfer colitis. J Leukoc Biol. 2004;76:1111-7 pubmed
    ..Thus, IL-6 might be a promising target for treating transmural inflammation in Crohn's disease, which can lead to severe complications such as strictures, fissures, and fistulas. ..
  55. Hayashi M, Shimba S, Tezuka M. Characterization of the molecular clock in mouse peritoneal macrophages. Biol Pharm Bull. 2007;30:621-6 pubmed
    ..The results obtained in this study indicate that the innate immunoreactions involving macrophages are at least partly regulated by the autonomous clock machinery. ..
  56. Lattanzio G, Libert C, Aquilina M, Cappelletti M, Ciliberto G, Musiani P, et al. Defective development of pristane-oil-induced plasmacytomas in interleukin-6-deficient BALB/c mice. Am J Pathol. 1997;151:689-96 pubmed
  57. Kovalchuk A, Kim J, Park S, Coleman A, Ward J, Morse H, et al. IL-6 transgenic mouse model for extraosseous plasmacytoma. Proc Natl Acad Sci U S A. 2002;99:1509-14 pubmed
    ..These findings provide a unique model of extramedullary PCT for studies on pathogenesis and treatment and suggest a previously unappreciated role for IL-6 in the genesis of germinal center-derived lymphomas. ..
  58. Carey A, Steinberg G, Macaulay S, Thomas W, Holmes A, Ramm G, et al. Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes. 2006;55:2688-97 pubmed
    ..Our results demonstrate that acute IL-6 treatment enhances insulin-stimulated glucose disposal in humans in vivo, while the effects of IL-6 on glucose and fatty acid metabolism in vitro appear to be mediated by AMPK. ..
  59. Beurel E, Jope R. Lipopolysaccharide-induced interleukin-6 production is controlled by glycogen synthase kinase-3 and STAT3 in the brain. J Neuroinflammation. 2009;6:9 pubmed publisher
    ..To identify potential targets to control brain IL-6, we tested if IL-6 produced by glia is regulated by signal transducer and activator of transcription-3 (STAT3) and glycogen synthase kinase-3 (GSK3)...
  60. White J, Reecy J, Washington T, Sato S, Le M, Davis J, et al. Overload-induced skeletal muscle extracellular matrix remodelling and myofibre growth in mice lacking IL-6. Acta Physiol (Oxf). 2009;197:321-32 pubmed publisher
    ..However, MyoD mRNA expression in 3 day OV IL-6(-/-) muscle was attenuated when compared with WT OV mice. IL-6 appears to be necessary for the normal regulation of extracellular matrix remodelling during OV-induced growth. ..
  61. Harker J, Lewis G, Mack L, Zuniga E. Late interleukin-6 escalates T follicular helper cell responses and controls a chronic viral infection. Science. 2011;334:825-9 pubmed publisher
    ..This resulted in escalation of germinal center reactions and improved antibody responses. Our results uncover an antiviral strategy that helps to safely resolve a persistent infection in vivo...
  62. Garbers C, Spudy B, Aparicio Siegmund S, Waetzig G, Sommer J, Holscher C, et al. An interleukin-6 receptor-dependent molecular switch mediates signal transduction of the IL-27 cytokine subunit p28 (IL-30) via a gp130 protein receptor homodimer. J Biol Chem. 2013;288:4346-54 pubmed publisher
    ..The binding of p28 to a gp130/Wsx-1 heterodimer or a gp130 homodimer is highly selective and controlled by a novel molecular switch induced by EBI3 or IL-6R, respectively. ..
  63. Van Snick J, Cayphas S, Vink A, Uyttenhove C, Coulie P, Rubira M, et al. Purification and NH2-terminal amino acid sequence of a T-cell-derived lymphokine with growth factor activity for B-cell hybridomas. Proc Natl Acad Sci U S A. 1986;83:9679-83 pubmed
  64. Klover P, Clementi A, Mooney R. Interleukin-6 depletion selectively improves hepatic insulin action in obesity. Endocrinology. 2005;146:3417-27 pubmed
    ..In conclusion, these results indicate that IL-6 plays an important and selective role in hepatic insulin resistance of obesity. ..
  65. Xu L, Kitani A, Fuss I, Strober W. Cutting edge: regulatory T cells induce CD4+CD25-Foxp3- T cells or are self-induced to become Th17 cells in the absence of exogenous TGF-beta. J Immunol. 2007;178:6725-9 pubmed
    ..They thus have important implications to our understanding of regulatory T cell function and their possible therapeutic use. ..
  66. Grivennikov S, Karin E, Terzic J, Mucida D, Yu G, Vallabhapurapu S, et al. IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell. 2009;15:103-13 pubmed publisher
    ..Proinflammatory cytokines have been suggested to regulate preneoplastic growth during CAC tumorigenesis. Interleukin 6 (IL-6) is a multifunctional NF-kappaB-regulated cytokine that acts on epithelial and immune cells...
  67. Adser H, Wojtaszewski J, Jakobsen A, Kiilerich K, Hidalgo J, Pilegaard H. Interleukin-6 modifies mRNA expression in mouse skeletal muscle. Acta Physiol (Oxf). 2011;202:165-73 pubmed publisher
    ..05) immediately after exercise only in IL-6 KO. In conclusion, IL-6 affects exercise-induced glycogen use, AMPK signalling and TNF-? mRNA responses in mouse skeletal muscle. ..
  68. Kopf M, Baumann H, Freer G, Freudenberg M, Lamers M, Kishimoto T, et al. Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature. 1994;368:339-42 pubmed
    ..We conclude that IL-6 production induced by injury or infection is an important in vivo SOS signal which coordinates activities of liver cells, macrophages and lymphocytes. ..
  69. Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, et al. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science. 2003;301:640-3 pubmed
    ..These findings demonstrate that TRIF is essential for TLR3- and TLR4-mediated signaling pathways facilitating mammalian antiviral host defense. ..
  70. Jenkins B, Roberts A, Greenhill C, Najdovska M, Lundgren May T, Robb L, et al. Pathologic consequences of STAT3 hyperactivation by IL-6 and IL-11 during hematopoiesis and lymphopoiesis. Blood. 2007;109:2380-8 pubmed
    We have previously demonstrated that STAT3 hyperactivation via the interleukin 6 (IL-6) cytokine family receptor gp130 in gp130 (Y757F/Y757F) mice leads to numerous hematopoietic and lymphoid pathologies, including neutrophilia, ..
  71. Tchivileva I, Tan K, Gambarian M, Nackley A, Medvedev A, Romanov S, et al. Signaling pathways mediating beta3-adrenergic receptor-induced production of interleukin-6 in adipocytes. Mol Immunol. 2009;46:2256-66 pubmed publisher
  72. Wu C, Hsieh C, Lin C, Chen W, Hong J, Chen M. Significance of IL-6 in the transition of hormone-resistant prostate cancer and the induction of myeloid-derived suppressor cells. J Mol Med (Berl). 2012;90:1343-55 pubmed publisher
    ..In conclusion, altered IL-6/STAT3 signaling is crucial in HR transition, aggressive behavior, and MDSC recruitment. These findings provide evidence for therapeutically targeting IL-6 signaling in prostate cancer. ..
  73. Bromander A, Ekman L, Kopf M, Nedrud J, Lycke N. IL-6-deficient mice exhibit normal mucosal IgA responses to local immunizations and Helicobacter felis infection. J Immunol. 1996;156:4290-7 pubmed
  74. Vallières L, Rivest S. Interleukin-6 is a needed proinflammatory cytokine in the prolonged neural activity and transcriptional activation of corticotropin-releasing factor during endotoxemia. Endocrinology. 1999;140:3890-903 pubmed
  75. Journiac N, Jolly S, Jarvis C, Gautheron V, Rogard M, Trembleau A, et al. The nuclear receptor ROR(alpha) exerts a bi-directional regulation of IL-6 in resting and reactive astrocytes. Proc Natl Acad Sci U S A. 2009;106:21365-70 pubmed publisher
    ..Thus, our findings indicate that ROR(alpha) is a pluripotent molecular player in constitutive and adaptive astrocyte physiology. ..
  76. Park E, Lee J, Yu G, He G, Ali S, Holzer R, et al. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell. 2010;140:197-208 pubmed publisher
    ..The chronic inflammatory response caused by obesity and enhanced production of IL-6 and TNF may also increase the risk of other cancers. ..
  77. Horii Y, Muraguchi A, Iwano M, Matsuda T, Hirayama T, Yamada H, et al. Involvement of IL-6 in mesangial proliferative glomerulonephritis. J Immunol. 1989;143:3949-55 pubmed
    ..These data suggest that deregulated production of IL-6 is involved in PGN and the measurement of urine IL-6 is helpful for the differential diagnosis of PGN as well as for monitoring the progression of PGN. ..
  78. Dalrymple S, Lucian L, Slattery R, McNeil T, Aud D, Fuchino S, et al. Interleukin-6-deficient mice are highly susceptible to Listeria monocytogenes infection: correlation with inefficient neutrophilia. Infect Immun. 1995;63:2262-8 pubmed
    ..Additionally, these data show a promising therapeutic potential for rIL-6 administration during opportunistic infection. ..
  79. Pasare C, Medzhitov R. Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science. 2003;299:1033-6 pubmed
    ..This block of suppressor activity was dependent in part on interleukin-6, which was induced by TLRs upon recognition of microbial products. ..
  80. Fäldt J, Wernstedt I, Fitzgerald S, Wallenius K, Bergstrom G, Jansson J. Reduced exercise endurance in interleukin-6-deficient mice. Endocrinology. 2004;145:2680-6 pubmed
    ..In summary, IL-6(-/-) mice have reduced endurance and energy expenditure during exercise, suggesting that IL-6 is necessary for normal exercise capacity. ..
  81. Schieffer B, Selle T, Hilfiker A, Hilfiker Kleiner D, Grote K, Tietge U, et al. Impact of interleukin-6 on plaque development and morphology in experimental atherosclerosis. Circulation. 2004;110:3493-500 pubmed
    ..These observations are consistent with the notion that baseline levels of IL-6 are required to modulate lipid homeostasis, vascular remodeling, and plaque inflammation in atherosclerosis. ..
  82. Kielar M, John R, Bennett M, Richardson J, Shelton J, Chen L, et al. Maladaptive role of IL-6 in ischemic acute renal failure. J Am Soc Nephrol. 2005;16:3315-25 pubmed
    ..It is concluded that macrophages infiltrate the area of the vascular bundles of the outer medulla, these macrophages produce IL-6, and this IL-6 exacerbates ischemic murine acute renal failure. ..
  83. Zheng Y, Danilenko D, Valdez P, Kasman I, Eastham Anderson J, Wu J, et al. Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature. 2007;445:648-51 pubmed
    ..IL-22, as an effector cytokine produced by T cells, mediates the crosstalk between the immune system and epithelial cells. ..
  84. Schirmacher P, Peters M, Ciliberto G, Blessing M, Lotz J, Meyer zum Buschenfelde K, et al. Hepatocellular hyperplasia, plasmacytoma formation, and extramedullary hematopoiesis in interleukin (IL)-6/soluble IL-6 receptor double-transgenic mice. Am J Pathol. 1998;153:639-48 pubmed
    ..Interestingly, the complex of IL-6 and the soluble interleukin 6 receptor (sIL-6R) activates target cells that do not express the membrane-bound IL-6R and therefore cannot ..
  85. Sun J, Sukhova G, Yang M, Wolters P, MacFarlane L, Libby P, et al. Mast cells modulate the pathogenesis of elastase-induced abdominal aortic aneurysms in mice. J Clin Invest. 2007;117:3359-68 pubmed
  86. Pflegerl P, Vesely P, Hantusch B, Schlederer M, Zenz R, Janig E, et al. Epidermal loss of JunB leads to a SLE phenotype due to hyper IL-6 signaling. Proc Natl Acad Sci U S A. 2009;106:20423-8 pubmed publisher
    ..In addition, we show that JunB(Deltaep) mice develop a SLE phenotype linked to increased epidermal interleukin 6 (IL-6) secretion. Intercrosses with IL-6-deficient mice could rescue the SLE phenotype...
  87. Croker B, Krebs D, Zhang J, Wormald S, Willson T, Stanley E, et al. SOCS3 negatively regulates IL-6 signaling in vivo. Nat Immunol. 2003;4:540-5 pubmed
    ..Our data indicate that SOCS3 and SOCS1 have reciprocal functions in IL-6 and IFN-gamma regulation and imply that SOCS3 has a role in preventing IFN-gamma-like responses in cells stimulated by IL-6. ..
  88. Kelly M, Keller C, Avilucea P, Keller P, Luo Z, Xiang X, et al. AMPK activity is diminished in tissues of IL-6 knockout mice: the effect of exercise. Biochem Biophys Res Commun. 2004;320:449-54 pubmed
    ..They also suggest that a genetic lack of IL-6 is associated with a decrease in AMPK activity. ..
  89. Yen D, Cheung J, Scheerens H, Poulet F, McClanahan T, McKenzie B, et al. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest. 2006;116:1310-6 pubmed
    ..This pathway may be responsible for chronic intestinal inflammation as well as other chronic autoimmune inflammatory diseases. ..
  90. Nurieva R, Chung Y, Hwang D, Yang X, Kang H, Ma L, et al. Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity. 2008;29:138-49 pubmed publisher
    ..This study thus demonstrates that Tfh is a distinct Th cell lineage. ..
  91. Diaz J, Booth A, Lu G, Wood S, Pinsky D, Bishop D. Critical role for IL-6 in hypertrophy and fibrosis in chronic cardiac allograft rejection. Am J Transplant. 2009;9:1773-83 pubmed publisher
    ..These observations reveal a new paradigm in which IL-6 drives development of pathologic hypertrophy and fibrosis in chronic cardiac allograft rejection and suggest that IL-6 could be a therapeutic target to prevent this disease. ..