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The Interleukin-1 Family: Back to the Future
Open accessAbstract
Interleukin-1 (IL-1) is a central mediator of innate immunity and inflammation. The IL-1 family includes seven ligands with agonist activity (IL-1α and IL-1β, IL-18, IL-33, IL-36α, IL-36β, IL-36γ), three receptor antagonists (IL-1Ra, IL-36Ra, IL-38), and an anti-inflammatory cytokine (IL-37). Members of the IL-1 Receptor (IL-1R) family include six receptor chains forming four signaling receptor complexes, two decoy receptors (IL-1R2, IL-18BP), and two negative regulators (TIR8 or SIGIRR, IL-1RAcPb). A tight regulation via receptor antagonists, decoy receptors, and signaling inhibitors ensures a balance between amplification of innate immunity and uncontrolled inflammation. All cells of the innate immune system express and/or are affected by IL-1 family members. Moreover, IL-1 family members play a key role in the differentiation and function of polarized innate and adaptive lymphoid cells. Here we will review the key properties of IL-1 family members, with emphasis on pathways of negative regulation and orchestration of innate and adaptive immunity.
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“In addition, NLRP3 inflammasome activation reduces phagocytosis of Aβ by microglial cells, thus increasing the Aβ depositions and contributing to the pathogenesis of AD (Garlanda et al., 2013; Gold and El Khoury, 2015).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Garlanda et al., 2013
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“Interleukin-18 is a member of the large interleukin-1 family40 that has recently been associated with cytokine storm disorders.”
From Cytokine storm (2020) · cites this paper as [40]
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Mantovani, A., Allavena, P., Sica, A., & Balkwill, F. (2008) · Nature · doi:10.1038/nature07205 · Cited by 11,399
Self-citationSuccinate is an inflammatory signal that induces IL-1β through HIF-1α
Tannahill, G. M., Curtis, A. M., Adamik, J., Palsson-McDermott, E. M., McGettrick, A. F., Goel, G., Frezza, C., Bernard, N. J., Kelly, B., Foley, N. H., et al. (2013) · Nature · doi:10.1038/nature11986 · Cited by 4,176 · cited 1×
“Accumulation of succinate in classically Immunity 39, December 12, 2013 ª2013 Elsevier Inc. 1005 activatedM1macrophages (Tannahill et al., 2013) stabilizes hypoxia-inducible factor a (HIF-1a), which in turn induces IL-1b.”
Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M., & Stockinger, B. (2006) · Immunity · doi:10.1016/j.immuni.2006.01.001 · Cited by 3,605 · cited 1×
“Accordingly, IL-1 is required for development of Th17 cell-sustained autoimmunity (e.g., Chung et al., 2009; Sutton et al., 2006; Veldhoen et al., 2006).”
Immunological and inflammatory functions of the interleukin-1 family
Dinarello, C. A. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132612 · Cited by 3,466 · cited 9×
“IL-1 affects virtually all cells and organs and is a major pathogenic mediator of autoinflammatory, autoimmune, infectious, and degenerative diseases (Dinarello, 2009, 2010; Dinarello et al., 2012; Gabay et al., 2010; Sims and Smith, 2010) (Table 2).”
InfluentialSelf-citationNeutrophils in the activation and regulation of innate and adaptive immunity
Mantovani, A., Cassatella, M. A., Costantini, C., & Jaillon, S. (2011) · Nature reviews. Immunology · doi:10.1038/nri3024 · Cited by 3,159 · cited 1×
“IL-1 markedly prolongs the lifespan and stimulates the effector function of neutrophils and macrophages (Mantovani et al., 2011).”
Non-canonical inflammasome activation targets caspase-11
Kayagaki, N., Warming, S., Lamkanfi, M., Walle, L. V., Louie, S., Dong, J., Newton, K., Qu, Y., Liu, J., Heldens, S., et al. (2011) · Nature · doi:10.1038/nature10558 · Cited by 2,530
Innate lymphoid cells — a proposal for uniform nomenclature
Spits, H., Artis, D., Colonna, M., Diefenbach, A., Disanto, J. D., Eberl, G., Koyasu, S., Locksley, R., McKenzie, A., Mebius, R., et al. (2013) · Nature reviews. Immunology · doi:10.1038/nri3365 · Cited by 2,380 · cited 4×
“The discovery of innate lymphoid cells and the dissection of pathways of T cell differentiation have revealed essential functions for IL-1, IL-18, and IL-33 and have opened vistas on their functions (O’Shea and Paul, 2010; Spits et al., 2013).”
InfluentialInterleukin-1 in the pathogenesis and treatment of inflammatory diseases
Dinarello, C. A. (2011) · Blood · doi:10.1182/blood-2010-07-273417 · Cited by 2,248 · cited 4×
“Extracellular cleavage of the inactive IL-1b precursor by neutrophil enzymes such a proteinase-3 and elastase generate active IL-1b because the cleavage site is close to that of caspase-1 (Dinarello, 2011).”
InfluentialNuocytes represent a new innate effector leukocyte that mediates type-2 immunity
Neill, D. R., Wong, S. H., Bellosi, A., Flynn, R. J., Daly, M. G., Langford, T. K. A., Bucks, C. M., Kane, C. M., Fallon, P. G., Pannell, R., et al. (2010) · Nature · doi:10.1038/nature08900 · Cited by 2,079 · cited 2×
“IL-33 plays a protective role against parasites ranging from nematode expulsion to control of Toxoplasma gondii encephalitis (Moro et al., 2010; Neill et al., 2010).”
A Large-Scale, Consortium-Based Genomewide Association Study of Asthma
Moffatt, M. F., Gut, I. G., Démenais, F., Strachan, D. P., Bouzigon, E., Heath, S. C., von Mutius, E., Farrall, M., Lathrop, M. G., & Cookson, W. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0906312 · Cited by 2,043 · cited 1×
“In humans, genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) in the genes encoding ST2 and IL-33 associated with asthma (Moffatt et al., 2010).”
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- Yousif, 2011, Expression of IL-37 in mouse protects the myocardium against ischemic injury via modulation of NF-κB activation, Circulation, 124, A8603
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Mayer-Barber, K. D., & Yan, B. (2016) · Cellular and Molecular Immunology · doi:10.1038/cmi.2016.25 · Cited by 210
The Role of IL‐1 β in the Bone Loss during Rheumatic Diseases
Ruscitti, P., Cipriani, P., Carubbi, F., Liakouli, V., Zazzeroni, F., Benedetto, P. D., Berardicurti, O., Alesse, E., & Giacomelli, R. (2015) · Mediators of Inflammation · doi:10.1155/2015/782382 · Cited by 211
“The inactive IL-1β precursor is cleaved by caspase-1 via a protein complex called inflammasome into an active cytokine [11].”
BackgroundResultMHCII-independent CD4+ T cells protect injured CNS neurons via IL-4.
Walsh, J. T., Hendrix, S., Boato, F., Smirnov, I., Zheng, J., Lukens, J. R., Gadani, S. P., Hechler, D., Gölz, G., Rosenberger, K., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci76210 · Cited by 208
“The IL-1 family of cytokines (IL-1α, IL-1β, IL-18, and IL-33) all signal in an MyD88-dependent manner (31) and may mediate the effect either collectively or synergistically.”
Kawano, Y., Nakae, J., Watanabe, N., Kikuchi, T., Tateya, S., Tamori, Y., Kaneko, M., Abe, T., Onodera, M., & Itoh, H. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.07.009 · Cited by 207
Cytokines IL-17 and IL-22 in the host response to infection
Valeri, M., & Raffatellu, M. (2016) · Pathogens and Disease · doi:10.1093/femspd/ftw111 · Cited by 202
“Intestinal cytokine responses comprise complex signaling networks, wherein cytokines regulate one another (Garlanda, Dinarello and Mantovani 2013; Manzanillo, Eidenschenk and Ouyang 2015) .”
BackgroundSohn, K. M., Lee, S., Kim, H. J., Cheon, S., Jeong, H., Lee, J.-Y., Kim, I. S., Silwal, P., Kim, Y. J., Paik, S., et al. (2020) · Journal of Korean Medical Science · doi:10.3346/jkms.2020.35.e343 · Cited by 199
Qian, S., Golubnitschaja, O., & Zhan, X. (2019) · The EPMA Journal · doi:10.1007/s13167-019-00194-x · Cited by 194
Koop, K., Backert, I., Wirtz, S. J., Hueber, A. J., Schett, G. A., Vieth, M. W., Probst, H. C., Bopp, T., Neurath, M. F., & Neufert, C. F. (2016) · Gut · doi:10.1136/gutjnl-2015-310374 · Cited by 192
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Tulotta, C., & Ottewell, P. D. (2018) · Endocrine Related Cancer · doi:10.1530/erc-17-0309 · Cited by 192
Response of host inflammasomes to viral infection
Chen, I.-Y., & Ichinohe, T. (2014) · Trends in Microbiology · doi:10.1016/j.tim.2014.09.007 · Cited by 198
β-amyloid, microglia, and the inflammasome in Alzheimer’s disease
Gold, M., & El Khoury, J. (2015) · Seminars in Immunopathology · doi:10.1007/s00281-015-0518-0 · Cited by 187
Kou, X., Xu, X., Chen, C., Sanmillan, M. L., Cai, T., Zhou, Y., Giraudo, C. G., Le, A. D., & Shi, S. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aai8524 · Cited by 191
Inflammatory outcomes of apoptosis, necrosis and necroptosis
Davidovich, P. B., Kearney, C. J., & Martin, S. J. (2014) · Biological Chemistry · doi:10.1515/hsz-2014-0164 · Cited by 190
“other members that remain to be fully characterized (Sims and Smith 2010; Garlanda et al., 2013).”
BackgroundCommandeur, A. E., Styer, A. K., & Teixeira, J. M. (2015) · Human Reproduction Update · doi:10.1093/humupd/dmv030 · Cited by 192
Martin, S. J. (2016) · FEBS Journal · doi:10.1111/febs.13775 · Cited by 188
Alternative Pathways of IL-1 Activation, and Its Role in Health and Disease
Pyrillou, K., Burzynski, L. C., & Clarke, M. C. H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.613170 · Cited by 202
Shouval, D. S., Biswas, A., Kang, Y. H., Griffith, A. E., Konnikova, L., Mascanfroni, I. D., Redhu, N. S., Frei, S. M., Field, M., Doty, A. L., et al. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.08.055 · Cited by 184
Clancy, D. M., Sullivan, G. P., Moran, H. B. T., Henry, C. M., Reeves, E. P., McElvaney, N. G., Lavelle, E. C., & Martin, S. J. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.062 · Cited by 186
“types, such as resident tissue macrophages and dendritic cells, epidermal keratinocytes, as well as endothelial cells lining local blood vessels (Garlanda et al., 2013; Afonina et al., 2015).”
BackgroundInfluentialRecent Advances: The Imbalance of Cytokines in the Pathogenesis of Inflammatory Bowel Disease
Guan, Q., & Zhang, J. (2017) · Mediators of Inflammation · doi:10.1155/2017/4810258 · Cited by 183
“IL-33 is widely expressed by many cell types, such as epithelial cells, fibroblasts, smooth muscle cells, and endothelial cells [66, 68].”
BackgroundInfluentialGasdermin D activity in inflammation and host defense
Lieberman, J., Wu, H., & Kagan, J. C. (2019) · Science Immunology · doi:10.1126/sciimmunol.aav1447 · Cited by 189
“One group of cytokines does not follow the path outlined above, members of which comprise some of the first cytokines identified: the interleukin-1 (IL-1) family (2).”
Interleukin-38 is released from apoptotic cells to limit inflammatory macrophage responses
Mora, J., Schlemmer, A., Wittig, I., Richter, F. M., Putyrski, M., Frank, A.-C., Han, Y., Jung, M., Ernst, A., Weigert, A., et al. (2016) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjw006 · Cited by 182
“IL-38 is N-terminally processed According to size and structure of the N-terminal pro-domain, IL-38 was assigned to the IL-36 subfamily (Garlanda et al., 2013; van de Veerdonk and Netea, 2013), whose members possess a consensus motif predicting a N-terminal cleavage site (for IL-38 after aa19) (Towne et al.”
BackgroundThe TLR and IL-1 signalling network at a glance
Cohen, P. (2014) · Journal of Cell Science · doi:10.1242/jcs.149831 · Cited by 186
“IL-33 stimulates Th2 cells, mast cells, eosinophils and basophils to produce type 2 cytokines, such as IL-4, IL-5 and IL-13, which stimulate the proliferation of B and T cells and have other important immune-modulatory functions (reviewed by Dinarello, 2011; Garlanda et al., 2013).”
BackgroundIL-33 in T Cell Differentiation, Function, and Immune Homeostasis
Peine, C., Marek, R. M., & Löhning, M. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.03.007 · Cited by 187
GSDMD is critical for autoinflammatory pathology in a mouse model of Familial Mediterranean Fever
Kanneganti, A., Malireddi, R. K. S., Saavedra, P. H. V., Walle, L. V., Gorp, H. V., Kambara, H., Sheppard, H., Vogel, P., Luo, H. R., Xavier, R. J., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20172060 · Cited by 182
“As key regulators of both innate and adaptive immunity, IL-1β and IL-18 not only are central to coordinating antimicrobial host defense, but these cytokines also play central roles in autoimmune and autoinflammatory diseases (Garlanda et al., 2013; Gurung and Kanneganti, 2016; Van Gorp et al., 2017).”
Binder, S., Luciano, M., & Horejs-Hoeck, J. (2018) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2018.08.004 · Cited by 190
Context-dependent role of IL-18 in cancer biology and counter-regulation by IL-18BP
Fabbi, M., Carbotti, G., & Ferrini, S. (2014) · Journal of Leukocyte Biology · doi:10.1189/jlb.5ru0714-360rr · Cited by 177
“which belongs to the IL-1 family [1].”
Roles of IL-1 in Cancer: From Tumor Progression to Resistance to Targeted Therapies
Gelfo, V., Romaniello, D., Mazzeschi, M., Sgarzi, M., Grilli, G., Morselli, A., Manzan, B., Rihawi, K., & Lauriola, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176009 · Cited by 182
“This activation leads to the expression of a large number of inflammatory genes [9,10].”
BackgroundEnninga, E. A. L., Nevala, W. K., Creedon, D. J., Markovic, S. N., & Holtan, S. G. (2014) · American Journal of Reproductive Immunology · doi:10.1111/aji.12303 · Cited by 171
Salivary cytokines as biomarkers of periodontal diseases
Jaedicke, K. M., Preshaw, P. M., & Taylor, J. J. (2015) · Periodontology 2000 · doi:10.1111/prd.12117 · Cited by 172
“The interleukin-1 cytokines are produced by a wide variety of cell types and perform critical functions in innate and adaptive immune responses to infection [36, 109].”
BackgroundAutonomic nervous system and inflammation interaction in endometriosis-associated pain
Wei, Y., Liang, Y., Lin, H., Dai, Y., & Yao, S. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01752-1 · Cited by 178
IL-1 mediates microbiome-induced inflammaging of hematopoietic stem cells in mice
Kovtonyuk, L. V., Caiado, F., Garcia-Martin, S., Manz, E.-M., Helbling, P., Takizawa, H., Boettcher, S., Al-Shahrour, F., Nombela-Arrieta, C., Slack, E., et al. (2022) · Blood · doi:10.1182/blood.2021011570 · Cited by 166
T-bet– and STAT4–dependent IL-33 receptor expression directly promotes antiviral Th1 cell responses
Baumann, C., Bonilla, W. V., Fröhlich, A., Helmstetter, C., Peine, C., Hegazy, A. N., Pinschewer, D. D., & Löhning, M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1418549112 · Cited by 175
“IL-33 acts on a wide range of immune cells, but has been implicated predominantly in Th2-associated immune responses (5).”
BackgroundThe P2X7 Receptor-Interleukin-1 Liaison
Giuliani, A. L., Sarti, A. C., Falzoni, S., & Di Virgilio, F. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00123 · Cited by 166
“Cytokines of the IL-1 family ligate and activate specific plasma membrane receptors, the IL-1 receptor family, comprised of 10 members, named IL-1R1, IL-1R2, IL-1R3 (IL-1RAcP), IL-R4 (ST2), IL-1R5 (IL-18Rα), IL-1R6 (IL-R36), IL-1R7 (IL-18Rβ), IL-1R8 (SIGIRR: single Ig IL-1R-related molecule or TIR8: three Ig domain-co…”
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Coll, R. C., & Schroder, K. (2024) · Nature reviews. Immunology · doi:10.1038/s41577-024-01075-9 · Cited by 175
“IL-1β activates many cell types and drives the expression of a large number of genes, including inflammatory cytokines, such as IL-6 and IL-8, and cyclooxygenase 2, ultimately causing systemic responses such as fever 175,176 .”
Targeting inflammation to reduce cardiovascular disease risk: A realistic clinical prospect?
Welsh, P., Grassia, G., Botha, S., Sattar, N., & Maffia, P. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13818 · Cited by 164
“It is the major pathogenic mediators of inflammatory and immune diseases (Garlanda et al., 2013; Schett et al., 2016).”
BackgroundInfluentialWu, T.-C., Xu, K., Martínek, J., Young, R. R., Banchereau, R., George, J., Turner, J., Kim, K. I., Zurawski, S., Wang, X., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-0413 · Cited by 168
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Nogueira, M., Puig, L., & Torres, T. R. (2020) · Drugs · doi:10.1007/s40265-020-01261-8 · Cited by 167
Castaño, Z., Juan, B. P. S., Spiegel, A., Pant, A., DeCristo, M. J., Laszewski, T., Ubellacker, J. M., Janssen, S. R., Dongre, A., Reinhardt, F., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0173-5 · Cited by 168
Bankova, L. G., Dwyer, D. F., Yoshimoto, E., Ualiyeva, S., McGinty, J. W., Raff, H., von Moltke, J., Kanaoka, Y., Austen, K. F., & Barrett, N. A. (2018) · Science Immunology · doi:10.1126/sciimmunol.aat9453 · Cited by 164
Zhivaki, D., Borriello, F., Chow, O. A., Doran, B. A., Fleming, I., Theisen, D. J., Pallis, P., Shalek, A. K., Sokol, C. L., Zanoni, I., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108381 · Cited by 170
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Polykratis, A., Martens, A., Eren, R. O., Shirasaki, Y., Yamagishi, M., Yamaguchi, Y., Uemura, S., Miura, M., Holzmann, B., Kollias, G. A., et al. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0324-3 · Cited by 162
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Creagh, E. M. (2014) · Trends in Immunology · doi:10.1016/j.it.2014.10.004 · Cited by 164
Zhang, J.-L., Ramadan, A., Griesenauer, B., Li, W., Turner, M., Liu, C., Kapur, R., Hanenberg, H., Blazar, B., Tawara, I., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aab0166 · Cited by 152
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Abreu, T. R., Fonseca, N. A., Gonçalves, N., & Moreira, J. N. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.12.047 · Cited by 159
Mohanty, A., Tiwari-Pandey, R., & Pandey, N. R. (2019) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-019-00507-9 · Cited by 164
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Evavold, C. L., & Kagan, J. C. (2019) · Immunity · doi:10.1016/j.immuni.2019.08.005 · Cited by 159
Liang, M., Chen, X., Wang, L., Qin, L., Wang, H., Sun, Z., Zhao, W., & Geng, B. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01688-7 · Cited by 159
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BackgroundCathepsin S is the major activator of the psoriasis-associated proinflammatory cytokine IL-36γ
Ainscough, J. S., Macleod, T., McGonagle, D., Brakefield, R., Baron, J. M., Alase, A., Wittmann, M., & Stacey, M. A. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620954114 · Cited by 155
Evidence of perturbations of the cytokine network in preterm labor
Romero, R. J., Grivel, J., Tarca, A. L., Chaemsaithong, P., Xu, Z., Fitzgerald, W., Hassan, S. S., Chaiworapongsa, T., & Margolis, L. B. (2015) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2015.07.037 · Cited by 150
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Hoß, F., Rodríguez-Alcázar, J. F., & Latz, E. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2396-6 · Cited by 158
“Inflammasome activation followed by caspase-1 activation, pyroptosis, and IL-1b release represents a very potent proinflammatory signal of the innate immune system [5, 77, 78].”
Maruzuru, Y., Ichinohe, T., Sato, R., Miyake, K., Okano, T., Suzuki, T., Koshiba, T., Koyanagi, N., Tsuda, S., Watanabe, M., et al. (2018) · Cell Host & Microbe · doi:10.1016/j.chom.2017.12.014 · Cited by 150
Libby, P. (2021) · Cells · doi:10.3390/cells10040951 · Cited by 158
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BackgroundFinethy, R., Jørgensen, I., Haldar, A. K., de Zoete, M. R., Strowig, T., Flavell, R. A., Yamamoto, M., Nagarajan, U. M., Miao, E. A., & Coers, J. (2015) · Infection and Immunity · doi:10.1128/iai.00856-15 · Cited by 150
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Henry, C. J., Casás-Selves, M., Kim, J., Zaberezhnyy, V., Aghili, L., Daniel, A. E., Jimenez, L., Azam, T., McNamee, E. N., Clambey, E. T., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci83024 · Cited by 148
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Boyapati, R. K., Rossi, A. G., Satsangi, J., & Ho, G. (2016) · Mucosal Immunology · doi:10.1038/mi.2016.14 · Cited by 150
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Evavold, C. L., & Kagan, J. C. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.09.019 · Cited by 155
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InfluentialCurrent perspectives on the role of interleukin-1 signalling in the pathogenesis of asthma and COPD
Osei, E. T., Brandsma, C., Timens, W., Heijink, I. H., & Hackett, T. (2019) · European Respiratory Journal · doi:10.1183/13993003.00563-2019 · Cited by 152
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Tsutsumi, N., Kimura, T., Arita, K., Ariyoshi, M., Ohnishi, H., Yamamoto, T. S., Zuo, X., Maenaka, K., Park, E. Y., Kondo, N., et al. (2014) · Nature Communications · doi:10.1038/ncomms6340 · Cited by 147
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InfluentialShared TIR enzymatic functions regulate cell death and immunity across the tree of life
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Libby, P., & Everett, B. M. (2019) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.118.310958 · Cited by 145
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Zhang, P., Tsuchiya, K., Kinoshita, T., Kushiyama, H., Suidasari, S., Hatakeyama, M., Imura, H., Katô, N., & Suda, T. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.743815 · Cited by 146
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BackgroundIL-1 Family Cytokine Pathways Underlying NAFLD: Towards New Treatment Strategies
Mirea, A.-M., Tack, C. J., Chavakis, T., Joosten, L. A. B., & Toonen, E. J. M. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.03.005 · Cited by 151
“In addition, IL-1β stimulates local inflammation by inducing production of IL-6, another pro-inflammatory cytokine (15).”
BackgroundFc-Optimized Anti-CCR8 Antibody Depletes Regulatory T Cells in Human Tumor Models
Campbell, J. R., McDonald, B., Mesko, P. B., Siemers, N. O., Singh, P. B., Selby, M., Sproul, T. W., Korman, A. J., Vlach, L. M., Houser, J., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-3585 · Cited by 140
“immunosuppressive adenosine (20), whereas CD25 and IL1R2 potentially act as sinks for proinflammatory cytokines IL2 (21) and IL1a/ b (22), respectively.”
BackgroundDolence, J. J., Kobayashi, T., Iijima, K., Krempski, J. W., Drake, L. Y., Dent, A. L., & Kita, H. (2017) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.11.020 · Cited by 144
“IL-1-family cytokine receptors are heterodimers, consisting of a specific receptor (eg, IL-1R1 and ST2) and a coreceptor, such as IL-1Rassociated protein (IL-1RAcP), which together form a high-affinity receptor complex.(42) Because IL-1RAcP is shared by IL-1R1 and ST2, we speculated that this coreceptor might be criti…”
Contact lens-related corneal infection: Intrinsic resistance and its compromise
Fleiszig, S. M. J., Kroken, A. R., Nieto, V., Grosser, M. R., Wan, S. J., Metruccio, M. M. E., & Evans, D. J. (2019) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2019.100804 · Cited by 143
Nishida, A., Hidaka, K., Kanda, T., Imaeda, H., Shioya, M., Inatomi, O., Bamba, S., Kitoh, K., Sugimoto, M., & Andoh, A. (2016) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000654 · Cited by 137
“The MyD88 adaptor complex is essential for IL-1–mediated signal transduction.(40) However, whether IL-36 cytokine binding to the IL-36R complex (IL-36R and IL-1RAcP) recruits MyD88 adaptor proteins has not been reported in previous studies.”
ResultT cell-intrinsic IL-1R signaling licenses effector cytokine production by memory CD4 T cells
Jain, A., Song, R., Wakeland, E. K., & Pasare, C. (2018) · Nature Communications · doi:10.1038/s41467-018-05489-7 · Cited by 137
Cutting Edge: Distinct Regulatory Mechanisms Control Proinflammatory Cytokines IL-18 and IL-1β
Zhu, Q., & Kanneganti, T. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700352 · Cited by 133
Mitochondria as a centrally positioned hub in the innate immune response
Sandhir, R., Halder, A., & Sunkaria, A. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.10.020 · Cited by 135
“PAMPs and DAMPs initiate an intricate set of signaling interactions releasing pro-inflammatory cytokines (IL-1β and IL-18) that prompt inflammatory response [15].”
Inflammasome biology, molecular pathology and therapeutic implications
Awad, F., Assrawi, E., Louvrier, C., Jumeau, C., Georgin‐Lavialle, S., Grateau, G., Amselem, S., Giurgea, I., & Karabina, S. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.02.011 · Cited by 138
NLRP3 Inflammasome: Checkpoint Connecting Innate and Adaptive Immunity in Autoimmune Diseases
Zhang, Y., Yang, W., Li, W., & Zhao, Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.732933 · Cited by 142
† (2015) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(15)00034-0 · Cited by 132
Cutting Edge: IL-36 Receptor Promotes Resolution of Intestinal Damage
Contreras, O. M., Harusato, A., Nishio, H., Flannigan, K. L., Ngo, V. L., Leoni, G., Neumann, P.-A., Geem, D., Lili, L. N., Ramadas, R. A., et al. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1501312 · Cited by 135
Interleukins 1 and 6 as main mediators of inflammation and cancer
Dmitrieva, O., Shilovskiy, I. P., Khaitov, M. R., & Grivennikov, S. I. (2016) · Biochemistry (Moscow) · doi:10.1134/s0006297916020024 · Cited by 137
IL-36α expression is elevated in ulcerative colitis and promotes colonic inflammation
Russell, S. E., Horan, R. M., Stefanska, A. M., Carey, A., León, G., Aguilera, M., Statovci, D., Moran, T., Fallon, P. G., Shanahan, F., et al. (2016) · Mucosal Immunology · doi:10.1038/mi.2015.134 · Cited by 133
Caffrey, A. K., Lehmann, M. M., Zickovich, J. M., Espinosa, V., Shepardson, K. M., Watschke, C. P., Hilmer, K. M., Thammahong, A., Barker, B. M., Rivera, A., et al. (2015) · PLOS Pathogens · doi:10.1371/journal.ppat.1004625 · Cited by 132
“IL1RI, together with IL1RAcP, is the high-afinity receptor for both IL-1αand IL-1β[27].”
InfluentialMao, C.-Y., Wang, Y.-G., Zhang, X., Zheng, X.-Y., Tang, T.-T., & Lu, E. Y. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.204 · Cited by 132
“Interleukin-1 (IL-1) is a pleiotropic cytokine and a central mediator of innate immunity and inflammation.(12) In clinical”
BackgroundInflammasomes and its importance in viral infections
Shrivastava, G., León‐Juárez, M., García‐Cordero, J., Meza-Sánchez, D. E., & Cedillo‐Barrón, L. (2016) · Immunologic Research · doi:10.1007/s12026-016-8873-z · Cited by 135
“In this context, the expression of proinflammatory cytokines such as interleukin (IL)-1b and IL-18 is induced by proinflammatory stimuli, including the activity of some PAMPs that can induce the synthesis of chemokines and adhesion molecules, resulting in the activation of a proinflammatory immune response [12].”
BackgroundAtherosclerosis: a chronic inflammatory disease mediated by mast cells
Conti, P., & Shaik-Dasthagirisaeb, Y. (2015) · Central European Journal of Immunology · doi:10.5114/ceji.2015.54603 · Cited by 135
T Cell Subsets in Graft Versus Host Disease and Graft Versus Tumor
Jiang, H., Fu, D., Bidgoli, A., & Paczesny, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.761448 · Cited by 136
Inoue, Y., Shirasuna, K., Kimura, H. J., Usui, F., Kawashima, A., Karasawa, T., Tago, K., Dezaki, K., Nishimura, S., Sagara, J., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302039 · Cited by 127
“Because IL1b and IL-1R signaling is critical for the induction of adhesion molecules required for the attachment of neutrophils to vascular endothelial cells (26), the inflammasome activation may influ-”
BackgroundYang, Y., Chou, W., Widowati, D. A., Lin, I.-P., & Peng, C. (2018) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-018-2267-9 · Cited by 128
The Antisocial Network: Cross Talk Between Cell Death Programs in Host Defense
Snyder, A. G., & Oberst, A. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-112019-072301 · Cited by 129
Innate immune detection of lipid oxidation as a threat assessment strategy
Zhivaki, D., & Kagan, J. C. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00618-8 · Cited by 129
Chen, W., Chen, S., Yan, C., Zhang, Y., Zhang, R., Chen, M., Zhong, S., Fan, W., Zhu, S., Zhang, D., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01255-6 · Cited by 132
IL-1 family cytokines in inflammation and immunity
Garlanda, C., Ceglie, I. D., & Jaillon, S. (2025) · Cellular and Molecular Immunology · doi:10.1038/s41423-025-01358-8 · Cited by 153
“1) [1, 2].”
InfluentialCarta, S., Penco, F., Lavieri, R., Martini, A., Dinarello, C. A., Gattorno, M., & Rubartelli, A. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1424741112 · Cited by 121
Cytokines: Roles in Atherosclerosis Disease Progression and Potential Therapeutic Targets
Moss, J. W. E., & Ramji, D. P. (2016) · Future Medicinal Chemistry · doi:10.4155/fmc-2016-0072 · Cited by 129
Ponce, D. M., Hilden, P. D., Mumaw, C. L., Devlin, S. M., Lubin, M. N., Giralt, S. A., Goldberg, J. D., Hanash, A. M., Hsu, K. C., Jenq, R. R., et al. (2014) · Blood · doi:10.1182/blood-2014-06-584789 · Cited by 125
“9 50 30% (18-43) BLOOD, 1 JANUARY 2015 x VOLUME 125, NUMBER 1 PROGNOSTIC IMPORTANCE OF ST2 LEVELS IN CBT 201 For personal use only.”
BackgroundThe immune network in thyroid cancer
Galdiero, M. R., Varricchi, G., & Marone, G. (2016) · OncoImmunology · doi:10.1080/2162402x.2016.1168556 · Cited by 124
“) and cytokines (IL-6, TNF-a, and TGF-b).(8) IL-1 stimulated thyroid cell proliferation and the in vitro production of IL-8.”
BackgroundThe Interleukin-1 (IL-1) Superfamily Cytokines and Their Single Nucleotide Polymorphisms (SNPs)
Behzadi, P., Aga, S. S., Nissar, S., Banday, M. Z., Gajdács, M., García‐Perdomo, H. A., Akhtar, K., Pinheiro, M., Magnusson, P., Sarshar, M., et al. (2022) · Journal of Immunology Research · doi:10.1155/2022/2054431 · Cited by 132
“Decoy receptors are conserved evolutionary structures which restrict the chemokines, cytokines, and growth factors activities [45 – 48, 68, 128, 129, 134].”
InfluentialEndocytic regulation of cytokine receptor signaling
Cendrowski, J., Mamińska, A., & Miączyńska, M. (2016) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2016.07.002 · Cited by 133
“The IL-1 receptor (IL-1R) superfamily contains several transmembrane protein complexes including 4 signaling receptors, IL-1, IL-18, IL-33 and IL-36 receptors [96].”
BackgroundThe role of the interleukin‐1 family in trained immunity
Moorlag, S. J. C. F. M., Röring, R. J., Joosten, L. A. B., & Netea, M. G. (2017) · Immunological Reviews · doi:10.1111/imr.12617 · Cited by 129
Management and potentialities of primary cancer cultures in preclinical and translational studies
Miserocchi, G., Mercatali, L., Liverani, C., Vita, A. D., Spadazzi, C., Pieri, F., Bongiovanni, A., Recine, F., Amadori, D., & Ibrahim, T. (2017) · Journal of Translational Medicine · doi:10.1186/s12967-017-1328-z · Cited by 126
Cytokines and fatty liver diseases
Niederreiter, L., & Tilg, H. (2018) · Liver Research · doi:10.1016/j.livres.2018.03.003 · Cited by 127
NOD-Like Receptor Protein 3 Inflammasome-Dependent IL-1β Accelerated ConA-Induced Hepatitis
Luan, J., Zhang, X., Wang, S., Li, Y., Fan, J., Chen, W., Zai, W., Wang, S., Wang, Y., Chen, M., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00758 · Cited by 123
Ngo, V. L., Abo, H., Maxim, E., Harusato, A., Geem, D., Contreras, O. M., Merlin, D., Gewirtz, A. T., Nusrat, A., & Denning, T. L. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1718902115 · Cited by 123
Function and Regulation of IL-36 Signaling in Inflammatory Diseases and Cancer Development
Queen, D., Ediriweera, C., & Liu, L. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00317 · Cited by 126
Pyroptosis-Induced Inflammation and Tissue Damage
Wei, Y., Yang, L., Pandeya, A., Cui, J., Zhang, Y., & Li, Z. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167301 · Cited by 130
Interleukin‐18 and diabetic nephropathy: A review
Yaribeygi, H., Atkin, S. L., & Sahebkar, A. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27427 · Cited by 121
Metadata
- Authors
- Garlanda, C., Dinarello, C. A., & Mantovani, A.
- Affiliations
- Radboud University Medical Center (NL)
- University of Milan (IT)
- Corresponding author
- Mantovani, Alberto
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 39
- Issue
- 6
- Pages
- 1003-1018
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC3933951
- OpenAlex
- W2145866317
- Cited by
- 1,945
- References
- 151
- Citations by year
- 2026: 80 · 2025: 118 · 2024: 136 · 2023: 122 · 2022: 168 · 2021: 172 · 2020: 202 · 2019: 165 · 2018: 194 · 2017: 192 · 2016: 171 · 2015: 156 · 2014: 66 · 2013: 1
- FWCI
- 11.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- European Research Council
- Associazione Italiana per la Ricerca sul Cancro
- National Institutes of Health (A115614, AR-45584)
- European Commission (FP7-HEALTH-2011- ADITEC 280873)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- 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 family, innate immunity, inflammation, IL-1 receptor family, interleukin-1 receptor antagonist, decoy receptor, IL-18, IL-33, IL-36, IL-37, IL-38, IL1RAP, SIGIRR, negative regulation of cytokine signaling, lymphocyte differentiation, innate and adaptive immunity
- MeSH terms
- Animals, Gene Expression Regulation, Humans, Immunity, Innate, Interleukin-1, Interleukins, Ligands, Receptors, Interleukin-1, Adaptive Immunity
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