The interleukin‐1 family: 10 years of discovery 1
Abstract
Ten years ago the cloning of two interleukin-1 molecules (IL-1 alpha and IL-1 beta) resolved the question of whether a single polypeptide could evoke a wide variety of biological effects. During the past decade, the biology of IL-1 has greatly expanded our understanding of how the host responds to external challenges, such as injury and infection, as well as its role in several diseases. We learned of the remarkable potency of IL-1 in the femtomolar range and of its ability to induce a response by triggering only one or two receptors per cell. Unexpectedly, the IL-1 family of genes, receptors and associated molecules have been linked to those of Drosophila, nematodes, and microorganisms and IL-1 signal transduction is similar to that observed after cellular stress. The cloning of IL-1 opened other avenues of fundamental biological interest. For example, in addition to the two agonist molecules IL-1 alpha and IL-1 beta, a third member of the IL-1 gene family is a specific, high affinity receptor antagonist (IL-1 receptor antagonist). That this third member of the IL-1 family inhibits the other two is characteristic of the tight control over production and activity exerted on IL-1. Although IL-1 contributes to the pathogenesis of many diseases, a small amount appears to be needed to combat infection and initiate healing processes. This article highlights 10 years of discoveries on IL-1.
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IL-1ra inhibits IL-1β signal transduction.
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“IL-1RA inhibits IL-1β signal transduction126”
From Exerkines in health, resilience and disease (2022) · cites this paper as [126]
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Wang, H., Bloom, O., Zhang, M., Vishnubhakat, J. M., Ombrellino, M., Che, J., Frazier, A., Yang, H., Ivanova, S., Borovikova, L. V., et al. (1999) · Science · doi:10.1126/science.285.5425.248 · Cited by 3,386 · see citing works
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Feldmann, M., Brennan, F. M., & Maini, R. N. (1996) · Annual Review of Immunology · doi:10.1146/annurev.immunol.14.1.397 · Cited by 2,486 · see citing works
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Choy, E., & Panayi, G. S. (2001) · New England Journal of Medicine · doi:10.1056/nejm200103223441207 · Cited by 2,248 · see citing works
Grivennikov, S., Karin, E., Terzic, J., Mucida, D., Yu, G.-Y., Vallabhapurapu, S., Scheller, J., Rose-John, S., Cheroutre, H., Eckmann, L., et al. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.01.001 · Cited by 2,155 · see citing works
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Kuida, K., Lippke, J. A., Ku, G., Harding, M. W., Livingston, D. J., Su, M. S. S., & Flavell, R. A. (1995) · Science · doi:10.1126/science.7535475 · Cited by 1,606 · see citing works
Regulation of intestinal epithelial permeability by tight junctions
Suzuki, T. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1070-x · Cited by 1,365 · see citing works
“In intestinal Caco-2 cells, IL-1b decreases TER and increases inulin flux [116, 117].”
BackgroundInfluentialAnti-TNFα Therapy of Rheumatoid Arthritis: What Have We Learned?
Feldmann, M., & Maini, R. N. (2001) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.163 · Cited by 1,252 · see citing works
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Wang, H., Liao, H., Ochani, M., Justiniani, M., Lin, X., Yang, L., Al-Abed, Y., Wang, H., Metz, C., Miller, E. J., et al. (2004) · Nature Medicine · doi:10.1038/nm1124 · Cited by 1,170 · see citing works
Dangerous liaisons: STAT3 and NF-κB collaboration and crosstalk in cancer
Grivennikov, S. I., & Karin, M. (2010) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2009.11.005 · Cited by 1,160 · see citing works
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Yang, H., Ochani, M., Li, J., Qiang, X., Tanovic, M., Harris, H. E., Susarla, S. M., Ulloa, L., Wang, H., DiRaimo, R., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2434651100 · Cited by 1,126 · see citing works
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Ferrari, D., Pizzirani, C., Adinolfi, E., Lemoli, R. M., Curti, A., Idzko, M., Panther, E., & Di Virgilio, F. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.7.3877 · Cited by 1,025 · see citing works
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BackgroundIL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology
Tat, S. K., Marc, P., Théoleyre, S., Heymann, D., & Fortun, Y. (2004) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2003.10.005 · Cited by 959 · see citing works
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Chow, L. S., Gerszten, R. E., Taylor, J. M., Pedersen, B. K., van Praag, H., Trappe, S., Febbraio, M. A., Galis, Z. S., Gao, Y., Haus, J. M., et al. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00641-2 · Cited by 927 · see citing works
IRAK: A Kinase Associated with the Interleukin-1 Receptor
Cao, Z., Henzel, W. J., & Gao, X. (1996) · Science · doi:10.1126/science.271.5252.1128 · Cited by 898 · see citing works
IL-1 pathways in inflammation and human diseases
Gabay, C., Lamacchia, C., & Palmer, G. (2010) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2010.4 · Cited by 897 · see citing works
Intestinal Permeability Regulation by Tight Junction: Implication on Inflammatory Bowel Diseases
Lee, S. H. (2015) · Intestinal Research · doi:10.5217/ir.2015.13.1.11 · Cited by 810 · see citing works
“Interleukin-1β (IL-1β) is markedly elevated in intestinal mucosa under inflammatory conditions, such as CD patients.(44) In clinical studies, an IL-1 receptor antagonist is currently being developed for therapeutic usage, which indicates IL-1β plays a central role in the intestinal inflammatory process.”
BackgroundInflammatory Cytokines in Experimental and Human Stroke
Lambertsen, K., Biber, K., & Finsen, B. (2012) · Journal of Cerebral Blood Flow and Metabolism · doi:10.1038/jcbfm.2012.88 · Cited by 730 · see citing works
“…TNF-Rs and IL-1Rs, and IL-6R (Allan et al, 2005; McCoy and Tansey, 2008; Suzuki et al, 2009), however, baseline expression may, as has been estimated for the IL-1RI, be limited to very few receptors per cell (Dinarello, 1994), which makes it difficult to study their expression in tissue sections.”
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Azuma, Y., Kaji, K., Katogi, R., Takeshita, S., & Kudo, A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.7.4858 · Cited by 731 · see citing works
Ceppi, M., Pereira, P. M., Dunand-Sauthier, I., Barras, E., Reith, W., Santos, M. A. S., & Pierre, P. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811073106 · Cited by 718 · see citing works
“In this context, IL-1 forms an important part of the inflammatory response, increasing the expression of adhesion factors on endothelial cells to enable transmigration of leukocytes to sites of infection (35).”
BackgroundThe Role of Cytokines in the Pathogenesis of Acute Pancreatitis
Norman, J. (1998) · The American Journal of Surgery · doi:10.1016/s0002-9610(97)00240-7 · Cited by 709 · see citing works
The Role of Markers of Inflammation in Traumatic Brain Injury
Woodcock, T. M., & Morganti-Kossmann, M. C. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00018 · Cited by 719 · see citing works
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BackgroundThe role of interleukin-1 in general pathology
Kaneko, N., Kurata, M., Yamamoto, T., Morikawa, S., & Masumoto, J. (2019) · Inflammation and Regeneration · doi:10.1186/s41232-019-0101-5 · Cited by 616 · see citing works
“They are also expressed in cellular subepithelial endometrial tissue of the uterus, in the glomeruli, in outer cortical areas of the kidney, and in various specific cell types, including neutrophils, keratinocytes, epithelial and endothelial cells, lymphocytes, smooth muscle cells, and fibroblasts [74, 75] .”
BackgroundThe Corneal Wound Healing Response:
Wilson, S. E., Mohan, R. R., Mohan, R. R., Ambrósio, R., Hong, J., & Lee, J. (2001) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(01)00008-8 · Cited by 612 · see citing works
Anti-inflammatory effects of exercise: role in diabetes and cardiovascular disease
Pedersen, B. K. (2017) · European Journal of Clinical Investigation · doi:10.1111/eci.12781 · Cited by 617 · see citing works
How we detect microbes and respond to them: the Toll-like receptors and their transducers
Beutler, B., Hoebe, K. H. N., Du, X., & Ulevitch, R. J. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.0203082 · Cited by 592 · see citing works
“In Drosophila, Toll was shown to be required for defense against fungal infection [24]; in mammals, IL-1 and IL-18 were known to be involved in innate and adaptive immune responses [25].”
BackgroundThe role of interleukin-1 in the pathogenesis of IDDM
Mandrup-Poulsen, T. R. (1996) · Diabetologia · doi:10.1007/bf00400649 · Cited by 543 · see citing works
Tumour necrosis factor-α induces ectopic activity in nociceptive primary afferent fibres
Sorkin, L. S., Xiao, W.-H., Wagner, R., & Myers, R. R. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00147-4 · Cited by 503 · see citing works
Respiratory Health Hazards in Agriculture
(1998) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.158.supplement_1.rccm1585s1 · Cited by 495 · see citing works
Cytokines in Inflammatory Bowel Disease
Rogler, G., & Andus, T. (1998) · World Journal of Surgery · doi:10.1007/s002689900401 · Cited by 483 · see citing works
Rietschel, E., Brade, H., Holst, O., Brade, L., Müller‐Loennies, S., Mamat, U., Zähringer, U., Beckmann, F., Seydel, U., Brandenburg, K., et al. (1996) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-80186-0_3 · Cited by 469 · see citing works
The vagus nerve and the nicotinic anti-inflammatory pathway
Ulloa, L. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1797 · Cited by 467 · see citing works
Baud, V., Liu, Z.-G., Bennett, B. L., Suzuki, N., Xia, Y., & Karin, M. (1999) · Genes & Development · doi:10.1101/gad.13.10.1297 · Cited by 464 · see citing works
The ‘cytokine profile’: a code for sepsis
Ulloa, L., & Tracey, K. J. (2005) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2004.12.007 · Cited by 438 · see citing works
Mechanism of IL-1β-Induced Increase in Intestinal Epithelial Tight Junction Permeability
Al–Sadi, R., Ye, D., Dokładny, K., & Ma, T. Y. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.8.5653 · Cited by 419 · see citing works
Keratoconus: an inflammatory disorder?
Galvis, V., Sherwin, T., Tello, A., Merayo, J., Barrera, R., & Acera, A. (2015) · Eye · doi:10.1038/eye.2015.63 · Cited by 398 · see citing works
Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders
Playford, R. J., MACDONALD, C. E., & Johnson, W. S. (2000) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/72.1.5 · Cited by 392 · see citing works
Identification and Initial Characterization of Four Novel Members of the Interleukin-1 Family
Kumar, S., McDonnell, P., Lehr, R. V., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.14.10308 · Cited by 366 · see citing works
IL-1 antagonism reduces hyperglycemia and tissue inflammation in the type 2 diabetic GK rat
Ehses, J. A., Lacraz, G., Giroix, M.-H., Schmidlin, F., Coulaud, J., Kassis, N., Irminger, J.-C., Kergoat, M., Portha, B., Homo-Delarche, F., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810087106 · Cited by 346 · see citing works
“Finally, IL-1 activity is known to increase the expression of chemokines in some tissues contributing to autoinflammatory diseases (38, 39).”
BackgroundStromal-epithelial interactions in the cornea
Wilson, S. E., Liu, J. J., & Mohan, R. R. (1999) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(98)00017-2 · Cited by 346 · see citing works
Jimi, E., Nakamura, I., Duong, L. T., Ikebe, T., Takahashi, N., Rodan, G. A., & Suda, T. (1999) · Experimental Cell Research · doi:10.1006/excr.1998.4320 · Cited by 329 · see citing works
Haskó, G., Kuhel, D. G., Nemeth, Z. H., Mabley, J. G., Stachlewitz, R. F., Virág, L., Lohinai, Z. M., Southan, G. J., Salzman, A. L., & Szabó, C. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.2.1013 · Cited by 333 · see citing works
Initiation of acute phase response and synthesis of cytokines
Koj, A. (1996) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(96)00048-8 · Cited by 330 · see citing works
Böni‐Schnetzler, M., Thorne, J. T., Parnaud, G., Marselli, L., Ehses, J. A., Kerr-Conte, J. A., Pattou, F. N., Halban, P. A., Weir, G. C., & Donath, M. Y. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0396 · Cited by 319 · see citing works
Theiler's Virus Infection: a Model for Multiple Sclerosis
Oleszak, E. L., Chang, J. R., Friedman, H. P., Katsetos, C. D., & Platsoucas, C. D. (2004) · Clinical Microbiology Reviews · doi:10.1128/cmr.17.1.174-207.2004 · Cited by 307 · see citing works
“It costimulates T- and B-cell responses (reviewed by Dinarello [105]) and is involved in induction of the expression of adhesion molecules and chemokines (67, 415).”
Convergence of IL-1β and VDR Activation Pathways in Human TLR2/1-Induced Antimicrobial Responses
Liu, P. T., Schenk, M., Walker, V. P., Dempsey, P. W., Kanchanapoomi, M., Wheelwright, M., Vazirnia, A., Zhang, X., Steinmeyer, A., Zügel, U., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005810 · Cited by 298 · see citing works
A primer on cytokines: sources, receptors, effects, and inducers
Curfs, J. H., Meis, J. F., & Hoogkamp-Korstanje, J. A. (1997) · Clinical Microbiology Reviews · doi:10.1128/cmr.10.4.742 · Cited by 317 · see citing works
Datta, S., & MacLean, R. R. (2007) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2007.02.004 · Cited by 296 · see citing works
“After pre-IL-1β is cleaved via IL-1β converting enzyme (ICE), the biologically active IL-1β is transported out of the cell (Dinarello, 1994;Obal and Krueger, 2003).”
BackgroundOrigin, differentiation and regulation of fetal and adult Leydig cells
Habert, R., Lejeune, H., & Saez, J. M. (2001) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(01)00461-0 · Cited by 292 · see citing works
Wang, H., Vishnubhakat, J. M., Bloom, O., Zhang, M., Ombrellino, M., Sama, A. E., & Tracey, K. J. (1999) · Surgery · doi:10.1016/s0039-6060(99)70182-0 · Cited by 298 · see citing works
Taming TNF: strategies to restrain this proinflammatory cytokine
Eigler, A., Sinha, B. N. M., Hartmann, G., & Endres, S. (1997) · Immunology Today · doi:10.1016/s0167-5699(97)01118-3 · Cited by 275 · see citing works
A newly defined interleukin-1?
Bazán, J. F., Timans, J. C., & Kastelein, R. A. (1996) · Nature · doi:10.1038/379591a0 · Cited by 283 · see citing works
Li, G., Bauer, S., Nowak, M., Norwood, B., Tackenberg, B., Rosenow, F., Knake, S., Oertel, W., & Hamer, H. (2011) · Seizure · doi:10.1016/j.seizure.2010.12.005 · Cited by 270 · see citing works
Intraarticular inflammatory cytokines in acute anterior cruciate ligament injured knee
入江, 一., Uchiyama, E., & Iwaso, H. (2003) · The Knee · doi:10.1016/s0968-0160(02)00083-2 · Cited by 270 · see citing works
The role of cytokines in inflammatory bone loss
de Souza, P. C., & Lerner, U. H. (2013) · Immunological Investigations · doi:10.3109/08820139.2013.822766 · Cited by 272 · see citing works
Rawat, M., Nighot, M., Al–Sadi, R., Gupta, Y. A., Viszwapriya, D., Yochum, G. S., Koltun, W. A., & Ma, T. Y. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.06.038 · Cited by 268 · see citing works
Bovine Colostrum: Its Constituents and Uses
Playford, R. J., & Weiser, M. J. (2021) · Nutrients · doi:10.3390/nu13010265 · Cited by 269 · see citing works
“Cytokines are not usually involved in normal cellular homeostasis, but become relevant at times of stress, inflammation, or injury [70], stimulating actions such as differentiation, chemotaxis and protein synthesis.”
BackgroundThe Natural History of the Anterior Cruciate Ligament-Deficient Knee
Cameron, M. L., Buchgraber, A., Pässler, H. H., et al. (1997) · The American Journal of Sports Medicine · doi:10.1177/036354659702500605 · Cited by 257 · see citing works
Mackowiak, P. A. (1998) · Archives of Internal Medicine · doi:10.1001/archinte.158.17.1870 · Cited by 254 · see citing works
Crofford, L. J., Tan, B., McCarthy, C. J., & Hla, T. (1997) · Arthritis & Rheumatism · doi:10.1002/art.1780400207 · Cited by 248 · see citing works
Anorexia during acute and chronic disease
Plata‐Saláman, C. R. (1996) · Nutrition · doi:10.1016/s0899-9007(96)90702-9 · Cited by 248 · see citing works
Schreuder, H., Tardif, C., Trump-Kallmeyer, S., Soffientini, A., Sarubbi, E., Akeson, A. L., Bowlin, T. L., Yanofsky, S. D., & Barrett, R. W. (1997) · Nature · doi:10.1038/386194a0 · Cited by 249 · see citing works
Rhee, S. H., & Hwang, D. H. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m007386200 · Cited by 247 · see citing works
Schülke, S. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00455 · Cited by 238 · see citing works
Macrophage-Osteoclast Associations: Origin, Polarization, and Subgroups
Sun, Y., Li, J., Xie, X., Gu, F., Sui, Z., Zhang, K., & Yu, T. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.778078 · Cited by 235 · see citing works
“The IL-1 gene family contains a number of different members, including: IL-1a, IL-1b, and the IL-1R antagonist (IL-1Ra) (69).”
BackgroundEffects of Clozapine on Plasma Cytokine and Soluble Cytokine Receptor Levels
Pollmächer, T., Hinze‐Selch, D., & Mullington, J. M. (1996) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-199610000-00011 · Cited by 232 · see citing works
Expression of bone-resorptive and regulatory cytokines in murine periapical inflammation
Kawashima, N., & Stashenko, P. (1999) · Archives of Oral Biology · doi:10.1016/s0003-9969(98)00094-6 · Cited by 223 · see citing works
“, 1994), these results indicate that IL1a plays a crucial part in bone destruction and lesional expansion, although the bioactivity of IL-1a may be modi®ed by IL-1receptor antagonist and IL-1 receptor type II, which were not assessed here (Dinarello, 1994).”
Interleukin-1 (IL-1) family of cytokines: Role in Type 2 Diabetes
Banerjee, M., & Saxena, M. (2012) · Clinica Chimica Acta · doi:10.1016/j.cca.2012.03.021 · Cited by 224 · see citing works
Wencker, M., Turchinovich, G., Barros, R. D. M., Deban, L., Jandke, A., Cope, A. P., & Hayday, A. (2013) · Nature Immunology · doi:10.1038/ni.2773 · Cited by 221 · see citing works
Insulin Attenuates the Systemic Inflammatory Response in Endotoxemic Rats
Jeschke, M. G., Klein, D., Bolder, U., & Einspanier, R. (2004) · Endocrinology · doi:10.1210/en.2004-0592 · Cited by 217 · see citing works
Al–Sadi, R., Ye, D., Said, H. M., & Ma, T. Y. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.100371 · Cited by 217 · see citing works
Chaudhary, P. M., Ferguson, C., Nguyen, V., Nguyen, O., Massa, H. F., Eby, M. T., Jasmin, A., Trask, B. J., Hood, L., & Nelson, P. S. (1998) · Blood · doi:10.1182/blood.v91.11.4020 · Cited by 213 · see citing works
T1/ST2 Signaling Establishes It as a Member of an Expanding Interleukin-1 Receptor Family
Mitcham, J. L., Parnet, P., Bonnert, T. P., Garka, K. E., GERHART, M. J., Slack, J. L., Gayle, M. A., Dower, S., & Sims, J. E. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.10.5777 · Cited by 210 · see citing works
Herath, S., Lilly, S. T., Santos, N. R., et al. (2009) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-7-55 · Cited by 202 · see citing works
Positive regulators of osteoclastogenesis and bone resorption in rheumatoid arthritis
Braun, T., & Zwerina, J. (2011) · Arthritis Research & Therapy · doi:10.1186/ar3380 · Cited by 202 · see citing works
Transcriptional Repression of the Prointerleukin 1β Gene by Heat Shock Factor 1
Cahill, C. M., Waterman, W. R., Xie, Y., Auron, P. E., & Calderwood, S. K. (1996) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)40087-7 · Cited by 198 · see citing works
Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAsPreprint
Lu, J., Sadri, N., & Schneider, R. J. (2006) · Genes & Development · doi:10.1101/gad.1467606 · Cited by 199 · see citing works
“The excessive production of these proinflammatory cytokines leads to systemic capillary leakage and vascular hemor- rhage, tissue destruction, and ultimately lethal organ failure and death (Tracey et al. 1987; Glauser et al. 1991; Dinarello 1994; Hotchkiss and Karl 2003; Martin et al. 2003).”
BackgroundInfluentialSchanstra, J. P., Bataillé, E., Castano, M. E. M., Barascud, Y., Hirtz, C., Pesquero, J. B., Pécher, C., Gauthier, F., Girolami, J., & Bascands, J. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1359 · Cited by 196 · see citing works
Cytokine Function: A Study in Biologic Diversity
Cohen, M. C., & Cohen, S. (1996) · American Journal of Clinical Pathology · doi:10.1093/ajcp/105.5.589 · Cited by 190 · see citing works
Toll-Like Receptor Signaling and Regulation of Cytokine Gene Expression in the Immune System
Ozato, K., Tsujimura, H., & Tamura, T. (2002) · BioTechniques · doi:10.2144/oct0208 · Cited by 189 · see citing works
Activation of NF-κB Is Involved in the Survival of Osteoclasts Promoted by Interleukin-1
Jimi, E., Nakamura, I., Ikebe, T., Akiyama, S., Takahashi, N., & Suda, T. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.15.8799 · Cited by 185 · see citing works
Croston, G. E., Cao, Z., & Goeddel, D. V. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.28.16514 · Cited by 182 · see citing works
Guan, Z., Baier, L. D., & Morrison, A. R. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.12.8083 · Cited by 180 · see citing works
Systemic inflammatory response syndrome (SIRS): molecular pathophysiology and gene therapy.
Matsuda, N., & Hattori, Y. (2006) · Journal of Pharmacological Sciences · doi:10.1254/jphs.crj06010x · Cited by 191 · see citing works
A critical role for interleukin‐1 receptor accessory protein in interleukin‐1 signaling
Korherr, C., Hofmeister, R., Wesche, H., & Falk, W. (1997) · European Journal of Immunology · doi:10.1002/eji.1830270139 · Cited by 175 · see citing works
Estrogens, inflammation and cognition
Au, A., Feher, A., McPhee, L., Jessa, A., Oh, S. J., & Einstein, G. (2016) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2016.01.002 · Cited by 175 · see citing works
“…are associated with an anti-inflammatory response such as the cytokines interleukin-10 (IL-10), which can inhibit NF-KB mediated upregulation of other cytokines (Clarke et al., 1998), or the IL- 1RA (interleukin-1 receptor antagonist) that inhibits the family of IL-1 cytokines (Dinarello, 1994).”
Neuroendocrine–immune interactions in fish: a role for interleukin-1
Engelsma, M. Y., Huising, M. O., van Muiswinkel, W. B., Flik, G., Kwang, J., Savelkoul, H. F. J., & Kemenade, B. M. L. V.-V. (2002) · Veterinary Immunology and Immunopathology · doi:10.1016/s0165-2427(02)00077-6 · Cited by 175 · see citing works
Role of cytokines in testicular function
Hales, D. B., Thorsten Diemer, A., & Hales, K. H. (1999) · Endocrine · doi:10.1007/bf02738619 · Cited by 173 · see citing works
Identification and Gene Organization of Three Novel Members of the IL-1 Family on Human Chromosome 2
Busfield, S. J., Comrack, C. A., Yu, G., Chickering, T. W., Smutko, J. S., Zhou, H., Leiby, K. R., Holmgren, L. M., Gearing, D. P., & Pan, Y. (2000) · Genomics · doi:10.1006/geno.2000.6184 · Cited by 173 · see citing works
Ishihara, Y., Nishihara, T., Kuroyanagi, T., Shirozu, N., Yamagishi, E., Ohguchi, M., Koide, M., Ueda, N., Amano, K., & Noguchi, T. (1997) · Journal of Periodontal Research · doi:10.1111/j.1600-0765.1997.tb00568.x · Cited by 168 · see citing works
Inflammasome activation and IL-1β target IL-1α for secretion as opposed to surface expression
Fettelschoss‐Gabriel, A., Kistowska, M., LeibundGut‐Landmann, S., Beer, H., Johansen, P., Senti, G., Contassot, E., Bachmann, M. F., French, L. E., Oxenius, A., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1109176108 · Cited by 169 · see citing works
“This cleavage depends on calpains, Ca-dependent proteases present at the cytosolic side of the cell membrane (6, 9, 10).”
Brough, D., Feuvre, R. A. L., Wheeler, R. D., Solovyova, N. A., Hilfiker, S., Rothwell, N. J., & Verkhratsky, A. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.6.3029 · Cited by 168 · see citing works
“Discussion The cytokine IL-1 is a key mediator of immune and inflammatory responses to injury and infection (25).”
BackgroundPinkerton, J., Kim, R., Robertson, A. A. B., Hirota, J. A., Wood, L. G., Knight, D. A., Cooper, M. A., O'Neill, L. A. J., Horvat, J. C., & Hansbro, P. M. (2017) · Molecular Immunology · doi:10.1016/j.molimm.2017.01.014 · Cited by 167 · see citing works
Doxycycline inhibition of interleukin-1 in the corneal epithelium.
Solomon, A., Rosenblatt, M. I., Li, D., Liu, Z., Monroy, D. C., Ji, Z., Lokeshwar, B. L., & Pflugfelder, S. C. (2000) · PubMed · Cited by 163 · see citing works
Interleukin-1 signal transduction
Bankers‐Fulbright, J. L., Kalli, K. R., & McKEAN, D. J. (1996) · Life Sciences · doi:10.1016/0024-3205(96)00135-x · Cited by 160 · see citing works
Apoptosis in the Cornea: Further Characterization of Fas/Fas Ligand System
Mohan, R. R., Liang, Q., Kim, W.-J., et al. (1997) · Experimental Eye Research · doi:10.1006/exer.1997.0371 · Cited by 157 · see citing works
Gastrointestinal Inflammation: A Central Component of Mucosal Defense and Repair
Martin, G. R., & Wallace, J. L. (2006) · Experimental Biology and Medicine · doi:10.1177/153537020623100202 · Cited by 156 · see citing works
Burdon, T. J., Paul, A., Noiseux, N., Prakash, S., & Tim, D. S. (2010) · Bone Marrow Research · doi:10.1155/2011/207326 · Cited by 158 · see citing works
“First of all, these are pro-inflammatory mediators, which are primarily synthesized by macrophages, monocytes, and dendritic cells, and are responsible for immune defense against infection in most tissues [114].”
BackgroundCytokine profiles of cultured microvascular endothelial cells from the human intestine
Nilsen, E. M., Johansen, F.-E., Jahnsen, F. L., Lundin, K. E. A., Scholz, T., Brandtzaeg, P., & Haraldsen, G. (1998) · Gut · doi:10.1136/gut.42.5.635 · Cited by 154 · see citing works
- Authors
- Dinarello, C. A.
- Affiliations
- Tufts University (US)
- Corresponding author
- Dinarello, Charles A.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 1994-12
- Volume
- 8
- Issue
- 15
- Pages
- 1314-1325
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W1514081838
- Cited by
- 783
- References
- 0
- Citations by year
- 2025: 8 · 2024: 8 · 2023: 8 · 2022: 14 · 2021: 17 · 2020: 21 · 2019: 14 · 2018: 11 · 2017: 19 · 2016: 17 · 2015: 23 · 2014: 27 · 2013: 23 · 2012: 26
- FWCI
- 18.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI‑15614)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- interleukin-1, IL-1α, IL-1β, interleukin-1 receptor antagonist, IL-1 receptor, Drosophila, nematodes, microorganisms, host response to infection, host response to injury, pathogenesis, cytokine regulation
- MeSH terms
- Animals, Humans, Interleukin-1, Structure-Activity Relationship, Signal Transduction, Receptors, Interleukin-1
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