Anakinra Therapy for Non-cancer Inflammatory Diseases.
TLDR
Anakinra has an unparalleled record of safety: opportunistic infections, particularly Mycobacterium tuberculosis, are rare even in populations at risk for reactivation of latent infections.Abstract:
Interleukin-1 (IL-1) is the prototypical inflammatory cytokine: two distinct ligands (IL-1α and IL-1β) bind the IL-1 type 1 receptor (IL-1R1) and induce a myriad of secondary inflammatory mediators, including prostaglandins, cytokines, and chemokines. IL-1α is constitutively present in endothelial and epithelial cells, whereas IL-1β is inducible in myeloid cells and released following cleavage by caspase-1. Over the past 30 years, IL-1-mediated inflammation has been established in a broad spectrum of diseases, ranging from rare autoinflammatory diseases to common conditions such as gout and rheumatoid arthritis (RA), type 2 diabetes, atherosclerosis, and acute myocardial infarction. Blocking IL-1 entered the clinical arena with anakinra, the recombinant form of the naturally occurring IL-1 receptor antagonist (IL-1Ra); IL-1Ra prevents the binding of IL-1α as well as IL-1β to IL-1R1. Quenching IL-1-mediated inflammation prevents the detrimental consequences of tissue damage and organ dysfunction. Although anakinra is presently approved for the treatment of RA and cryopyrin-associated periodic syndromes, off-label use of anakinra far exceeds its approved indications. Dosing of 100 mg of anakinra subcutaneously provides clinically evident benefits within days and for some diseases, anakinra has been used daily for over 12 years. Compared to other biologics, anakinra has an unparalleled record of safety: opportunistic infections, particularly Mycobacterium tuberculosis, are rare even in populations at risk for reactivation of latent infections. Because of this excellent safety profile and relative short duration of action, anakinra can also be used as a diagnostic tool for undefined diseases mediated by IL-1. Although anakinra is presently in clinical trials to treat cancer, this review focuses on anakinra treatment of acute as well as chronic inflammatory diseases.read more
Citations
More filters
Journal ArticleDOI
Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study.
Giulio Cavalli,Giacomo De Luca,Corrado Campochiaro,Emanuel Della-Torre,Marco Ripa,Diana Canetti,Chiara Oltolini,Barbara Castiglioni,Chiara Tassan Din,Nicola Boffini,Alessandro Tomelleri,Nicola Farina,Annalisa Ruggeri,Patrizia Rovere-Querini,Giuseppe Di Lucca,S. Martinenghi,Raffaella Scotti,Moreno Tresoldi,Fabio Ciceri,Giovanni Landoni,Alberto Zangrillo,Paolo Scarpellini,Lorenzo Dagna +22 more
TL;DR: In this retrospective cohort study of patients with COVID-19 and ARDS managed with non-invasive ventilation outside of the ICU, treatment with high-dose anakinra was safe and associated with clinical improvement in 72% of patients.
Journal ArticleDOI
Stellate Cells, Hepatocytes, and Endothelial Cells Imprint the Kupffer Cell Identity on Monocytes Colonizing the Liver Macrophage Niche
Johnny Bonnardel,Wouter T’Jonck,Djoere Gaublomme,Robin Browaeys,Charlotte L. Scott,Liesbet Martens,Bavo Vanneste,Sofie De Prijck,Sergei A. Nedospasov,Anna Kremer,Evelien Van Hamme,Peter Borghgraef,Wendy Toussaint,Pieter De Bleser,Inge Mannaerts,Alain Beschin,Leo A. van Grunsven,Bart N. Lambrecht,Tom Taghon,Saskia Lippens,Dirk Elewaut,Yvan Saeys,Martin Guilliams +22 more
TL;DR: It is shown that the Kupffer cell niche is composed of stellate cells, hepatocytes, and endothelial cells that together imprint the liver-specific macrophage identity.
Journal ArticleDOI
Immunopathogenesis and treatment of cytokine storm in COVID-19.
Jaeseok Kim,Jun Young Lee,Jae Won Yang,Keum Hwa Lee,Maria Effenberger,Wladimir Szpirt,Andreas Kronbichler,Jae Il Shin +7 more
TL;DR: The potential therapeutic role of extracorporeal cytokine removal to treat the cytokine storm associated with COVID-19 is discussed and expectations are especially high for new cytokine-targeted therapies, such as tocilizumab, anakinra, and baricitinib.
Journal ArticleDOI
The IL-1 family of cytokines and receptors in rheumatic diseases.
TL;DR: The main functions of the IL-1 family are innate immune reactions and inflammation, rather than acquired immunity, which can occur in several rheumatic diseases.
Journal ArticleDOI
Harnessing cytokines and chemokines for cancer therapy
TL;DR: The lessons learnt from the initial trials of single-agent cytokine-based therapies and subsequent efforts to better exploit such agents for the treatment of solid tumours are discussed.
References
More filters
Journal ArticleDOI
Inflammation and Atherosclerosis
TL;DR: New insights into inflammation in atherosclerosis not only increase the understanding of this disease, but also have practical clinical applications in risk stratification and targeting of therapy for this scourge of growing worldwide importance.
Journal ArticleDOI
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Paul M. Ridker,Brendan M. Everett,Tom Thuren,Jean G. MacFadyen,William Chang,Christie M. Ballantyne,Francisco H. Fonseca,Jose C. Nicolau,Wolfgang Koenig,Stefan D. Anker,John J.P. Kastelein,Jan H. Cornel,Prem Pais,Daniel Pella,Jacques Genest,Renata Cifkova,Alberto J. Lorenzatti,Tamás Forster,Zhanna Kobalava,Luminita Vida-Simiti,Marcus Flather,Hiroaki Shimokawa,Hisao Ogawa,Mikael Dellborg,Paulo Roberto Ferreira Rossi,Roland P.T. Troquay,Peter Libby,Robert J. Glynn +27 more
TL;DR: Antiinflammatory therapy targeting the interleukin‐1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid‐level lowering.
Journal ArticleDOI
Biologic basis for interleukin-1 in disease
TL;DR: This is a lengthy review, with 586 citations chosen to illustrate specific areas of interest rather than a compendium of references, which summarizes what the author considers established or controversial topics linking the biology of IL-1 to mechanisms of disease.
Journal ArticleDOI
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
Peter Duewell,Hajime Kono,Katey J. Rayner,Katey J. Rayner,Cherilyn M. Sirois,Gregory I. Vladimer,Franz Bauernfeind,George S. Abela,Luigi Franchi,Guillermo Gabriel Nuñez,Max Schnurr,Terje Espevik,Egil Lien,Katherine A. Fitzgerald,Kenneth L. Rock,Kathryn J. Moore,Kathryn J. Moore,Samuel D. Wright,Veit Hornung,Eicke Latz,Eicke Latz +20 more
TL;DR: It is shown that cholesterol crystals activate the NLRP3 inflammasome in phagocytes in vitro in a process that involves phagolysosomal damage and that crystalline cholesterol acts as an endogenous danger signal and its deposition in arteries or elsewhere is an early cause rather than a late consequence of inflammation.
Journal ArticleDOI
Type 2 diabetes as an inflammatory disease.
TL;DR: Preliminary results from clinical trials with salicylates and interleukin-1 antagonists support the notion that inflammation participates in the pathogenesis of type 2 diabetes and have opened the door for immunomodulatory strategies for the treatment of T2D that simultaneously lower blood glucose levels and potentially reduce the severity and prevalence of the associated complications of this disease.
Related Papers (5)
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
Chaolin Huang,Yeming Wang,Xingwang Li,Lili Ren,Jianping Zhao,Yi Hu,Li Zhang,Guohui Fan,Jiuyang Xu,Xiaoying Gu,Zhenshun Cheng,Ting Yu,Jia'an Xia,Yuan Wei,Wenjuan Wu,Xuelei Xie,Wen Yin,Li Hui,Min Liu,Yan Xiao,Hong Gao,Li Guo,Jungang Xie,Guang-Fa Wang,Rongmeng Jiang,Zhancheng Gao,Qi Jin,Jianwei Wang,Bin Cao +28 more
The Interleukin-1 Family: Back to the Future
Dexamethasone in Hospitalized Patients with Covid-19
Peter Horby,Wei Shen Lim,Jonathan Emberson,M Mafham,Jennifer L Bell,Louise Linsell,Natalie Staplin,Christopher E. Brightling,Andrew Ustianowski,E Elmahi,B Prudon,Christopher A Green,Timothy Felton,David Chadwick,K Rege,C Fegan,Lucy C Chappell,Saul N. Faust,Thomas Jaki,Katie Jeffery,Alan A Montgomery,Kathryn M Rowan,Edmund Juszczak,J K Baillie,Richard Haynes,Martin J Landray +25 more