Tumor Necrosis Factor alpha
Tumor Necrosis Factor alpha
Tumor Necrosis Factor alpha (TNF-a, also known as cachexin, or cachectin) is a systemic inflammatory response cytokine and is secreted primarily by macrophages and monocytes during acute inflammation. It is also produced by CD4+ lymphocytes, NK cells, neutrophils mast cells, eosinophils, and neurons. TNF is produced as a type II transmembrane protein. The metalloprotease TNF-a converting enzyme (TACE, also known as ADAM17) releases the homotrimeric cytokine from the membrane-bound form through proteolytic cleavage. The membrane-bound and soluble forms of the homotrimer bind to TNFR-1, expressed on most tissues. The membrane-bound form can also bind to TNFR-2, expressed primarily on immune cells. TNF plays a critical role in resistance to bacterial, viral, and parasitic infections and is responsible for a wide range of cellular process, including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. TNF regulates immune cells. As an endogenous pyrogen, TNF induces fever, apoptosis, and can inhibit tumorigenesis. The cytokine has been implicated in a multiple disease states, including autoimmune diseases, insulin resistance, and cancer. TNF dysregulation has been implicated in Alzheimer?s disease and psoriasis.
Swiss-Prot Accession Number: P01375
Bibliography
Peripheral immune cell imbalance is associated with cortical beta-amyloid deposition and longitudinal cognitive decline (2023) Neel H. Mehta, Liangdong Zhou, Yi Li, Laura Beth McIntire, Anna Nordvig, Tracy Butler, Mony de Leon & Gloria C. Chiang Nature
medical_services Therapy IndicationsPhase 1 dose-escalation study of SEA-CD40: a non-fucosylated CD40 agonist, in advanced solid tumors and lymphomas (2023) Andrew L Coveler, David C Smith, Tycel Phillips, Brendan D Curti, Sanjay Goel, Amitkumar N Mehta, Timothy M Kuzel, Svetomir N Markovic, Olivier Rixe, David L Bajor, Thomas F Gajewski, Martin Gutierrez, Hun Ju Lee, Ajay K Gopal, Paolo Caimi, Elisabeth I Heath, John A Thompson, Sahar Ansari, Celine Jacquemont, Ariel Topletz-Erickson, Peigen Zhou, Michael W Schmitt, Juneko E Grilley-Olson Journal for ImmunoTherapy of Cancer
medical_services Therapy IndicationsFirst-in-human study of the safety, tolerability, pharmacokinetics and pharmacodynamics of ALPN-101, a dual CD28/ICOS antagonist, in healthy adult subjects (2021) Yang J, Lickliter JD, Hilson JL, Means GD, Sanderson RJ, Carley K, Tercero A, Manjarrez KL, Wiley JR, Peng SL Clinical and Translational Science
medical_services Therapy IndicationsDevelopment of an affordable, sustainable and efficacious plant-based immunomodulatory food ingredient based on bell pepper or carrot RG-I pectic polysaccharides (2021) McKay S, Oranje P, Helin J, Koek JH, Kreijveld E, van den Abbeele P, Phol u, Bothe G, Tzoumaki M, Aparicio-Vergara M Nutrients
medical_services Therapy IndicationsVery-low-carbohydrate diet enhances human T-cell immunity through immunometabolic reprogramming (2021) Hirschberger S, Straub G, Effinger D, Marstaller X, Ferstl A, Muller MB, Wu T, Hubner M, Rahmel T, Mascolo H, Exner N, Heb J, Kreth FW, Unger K, Kreth S EMBO Molecular Medicine
medical_services Therapy IndicationsModulation of cardiometabolic disease markers by type I interferon inhibition in systemic lupus erythematosus (2020) Casey KA, Smith MA, Sinibaldi D, Seto NL, Playford MP, Wang X, Carlucci PM, Wang L, Illei G, Yu B, Wang S, Remaley AT, Mehta NH, Kaplan MJ, White WI Arthritis Rheumatology
medical_services Therapy IndicationsNasal Microbiota Modifies the Effects of Particulate Air Pollution on Plasma Extracellular Vesicles. (2020) Mariana J, Favero C, Carungno M, Pergoli L, Ferrari L, Bonzini M, Cattaneo A, Pesatori AC, Bollati V International Journal of Environmental Research and Public Health
medical_services Therapy IndicationsImmune profiling enables stratification of patients with active TB disease or M. tuberculosis infection (2020) Duffy D, Nemes E, Llibre A, Rouilly V, Musvosvi M, Smith N, Filander E, Africa H, Mabwe S, Jaxa L, Charbit B, Mulenga H, the Milieu Interieur Consortium, Tameris M, Walzl G, Malherbe S, Thomas S, Hatherill M, Bilek N, Scriba TJ, Albert ML Clinical Infectious Diseases
medical_services Therapy IndicationsTranscutaneous auricular vagus nerve stimulation reduces pain and fatigue in patients with systemic lupus erythematosus: a randomised, double-blind, sham-controlled pilot trial (2020) Aranow C, Atish-Fregoso Y, Lesser M, Mackay M, Anderson E, Chavan S, Zanos TP, Datta-Chaundhuri T, Bouton C, Tracey KJ, Diamond B Annals of the rheumatic diseases
medical_services Therapy IndicationsVaccHemInf Project: protocol for a prospective cohort study of efficacy, safety and characterisation of immune functional response to vaccinations in haematopoietic stem cell transplant recipients (2019) Conrad A, Boccard M, Valour F, Alcazer V, Tovar Sanchez AT, Chidiac C, Laurent F, Vanhems P, Salles G, Brengel-Pesce K, Meunier B, Trouillet-Assant S, Ader F, Lyyon HEMINF Study Group BMJ Journals
medical_services Therapy IndicationsMaternal deprivation increases microglial activiation and neuroinflammatory markers in the prefrontal cortex and hippocampus of infant rats (2019) Giridharan VV, Gislaine ZR, Selvaraj S, Scaini G, Barichello T, Quevedo J Journal of Psychiatric Research
medical_services Therapy IndicationsCereblon modulator iberdomide induces degradation of the transcription factor Ikaros and Aiolos: immunomodulation in healthy volunteers and relevance to systemic lupus erythematosus (2018) Schafer PH, Ye Y, Wu L, Kosek J, Ringheim G, Yang Z, Liu L, Thomas M, Palmisano M, Chopra R Ann Rheum Dis
medical_services Therapy IndicationsPEGylated IL-10 (Pegilodecakin) Induces Systemic Immune Activation, CD8+ T Cell Invigoration and Polyclonal T Cell Expansion in Cancer Patients (2018) Naing A, Infante JR, Papadopoulos KP, Chan IH, Shen C, Ratti NP, Autio KA, Wong DJ, Patel MR, Ott PA, Falchook GS, Pant S, Hung A, Pekarek KL, Wu V, Adamow M, McCauley S, Mumm JB, Wong P, Van Vlasselaer P, Levegue J, Tannir NM, Oft M Cancer Cell
medical_services Therapy IndicationsDominace rank-associated gene expression is widespread, sex-specific, and a precursor to high social status in wild male baboons (2018) Lea AJ, Akinyi MY, Nyakundi R, Mareri P, Kariuki T, Alberts SC, Archie EA, Tung J PNAS
medical_services Therapy IndicationsEvaluation of plasma biomarkers of inflammation in patients with maple syrup urine disease (2018) Scaini G, Tonon T, Moura de Souza CF, Schuck PF, Ferreira GC, Quevedo J, Seda Neto J, Amorim T, Camelo Jr JS, Vitoria Barban Margutti A, Hencke Tresbach R, Sperb-Ludwig F, Boy R, V. de Medeiros PF, Schwards IVD, Luiz Streck E Journal of Inherited Metabolic Disease
medical_services Therapy IndicationsThe role of anxious distress in immune dysregulation in patients with major depressive disorder. (2017) Gaspersz R, Lamers F, Wittenberg G, Beekman ATF, van Hemert AM, Schoevers RA, Penninx BWJH Transl Psychiatry
medical_services Therapy IndicationsDietary Buglossoides Arvensis Oil Increases Circulating n-3 Ployunsaturated Fatty Acids in a Dose Dependent Manner and Enhances Lipopolysaccharide-Stimulated Whole Blood Interleukin-10-A Randomized Placebo-Controlled Trial. (2017) Lefort N, LeBlanc R, Surette M Nutrients
medical_services Therapy IndicationsImmunodepression after CPB: Cytokine dynamics and clinics after pediatric cardiac surgery ? A prospective trial (2017) Justus G, Walker C, Rosenthal LM, Berger F, Miera O, Schmitt KR Cytokine
medical_services Therapy IndicationsProteomics to predict the response to tumour necrosis factor-a inhibitors in rheumatoid arthritis using a supervised cluster-analysis based protein score (2017) Cuppen BVJ, Fritsch-Stork RDE, Eekhout, W de Jager I, Marijnissen AC, Bijlsma JWJ, Custers M, Van Laar JM, Lafeber FPJG, Welsing PMJ & on behalf of all Society for Rheumatology Research Utrecht (SRU) investigators Scand J Rheumatol
medical_services Therapy IndicationsCharacterizing the Inflammatory Response in Esophageal Mucosal Biopsies in Children with Eosinophilic Esophagitis (2016) Sayej WN, Menoret A, Maharjan AS, Fernandez M, Wang Z, Balarezo F, Hyams JS, Sylvester FA, Vella AT Clinical & Translational Immunology
medical_services Therapy IndicationsDynamic Macrophage Polarization-Specific miRNA Patterns Reveal Increased Soluble VEGF Receptor 1 by miR-125a-5p Inhibition. (2016) Melton DW, Lei XF, Gelfond JAL, Shireman PK Physiological Genomics
medical_services Therapy IndicationsA Novel Approach for Emerging and Antibiotic Resistant Infections: Innate Defense Regulators as an Agnostic Therapy (2016) North JR, Takenaka S, Rozek A, Kielczewska A, Opal S, Morici LA, Finlay BB, Schaber CJ, Straube R, Donini O Journal of Biotechnology
medical_services Therapy IndicationsSystems Biology Reveals Cigarette Smoke-Induced Concentration-Dependent Direct and Indirect Mechanisms That Promote Monocyte-Endothelial Cell Adhesion. (2015) Poussin C, Laurent A, Peitsch MC, Hoeng J, De Leon H Toxicol Sci.
medical_services Therapy IndicationsA Phase 1 Dose-Finding Study of the Novel Toll-like Receptor 8 Agonist VTX 2337 in Adult Subjects with Advanced Solid Tumors or Lymphoma (2014) Northfelt DW, Ramanathan RK, Cohen PA, Von Hoff DD, Weiss GJ, Dietsch GN, Manjarrez KL, Randall TD, Hershberg RM Clin Cancer Res. 2014 May 7
medical_services Therapy IndicationsPharmacologic inhibition of S-nitrosoglutathione reductase protects against experimental asthma in BALB/c mice through attenuation of both bronchoconstriction and inflammation (2014) Blonder JP, Mutka SC, Sun X, Qiu J, Green LH, Mehra NK, Boyanapalli R, Suniga M, Look K, Delany C, Richards JP, Looker D, Scoggin C, Rosenthal GJ BMC Pulm Med. 2014 Jan 10;14(1):3
medical_services Therapy IndicationsSerum protein profiling reveals baseline and pharmacodynamic biomarker signatures associated with clinical outcome in mCRC patients treated with chemotherapy ? cediranib. (2014) Pommier AJ, Shaw R, Spencer SK, Morgan SR, Hoff PM, Robertson JD, Barry ST, J?rgensmeier JM. British Journal of Cancer 2014 Aug 14. doi: 10.1038/bjc.2014.436. [Epub ahead of print]
medical_services Therapy IndicationsCD47 fusion protein targets CD172a+ cells in Crohn?s disease and dampens the production of IL-1? and TNF (2013) Baba N, Van VQ, Wakahara K, Rubio M, Fortin G, Panzini B, Soucy G, Wassef R, Richard C, Tamaz R, Lahaie R, Bernard EJ, Caussignac Y, Leduc R, Lougnarath R, Bergeron C, Racicot MA, Bergeron F, Panzini MA, Demetter P, Franchimont D, Sch?kel K, Weckbecker G, Kolbinger F, Heusser C, Huber T, Welzenbach K, Sarfati M J Exp Med. 2013 May 13. [Epub ahead of print]
medical_services Therapy IndicationsApplicability of rat precision-cut lung slices in evaluating nanomaterial cytotoxicity, apoptosis, oxidative stress, and inflammation (2013) Sauer UG, Vogel S, Aumann A, Hess A, Kolle SN, Ma-Hock L, Wohlleben W, Dammann M, Strauss V, Treumann S, Gr?ters S, Wiench K, van Ravenzwaay B, Landsiedel R Toxicol Appl Pharmacol. 2013 Dec 29. pii: S0041-008X(13)00570-X
medical_services Therapy IndicationsTargeting oxidized LDL improves insulin sensitivity and immune cell function in obese Rhesus macaques (2013) Li S,Kievit P, Robertson A-K, Kolumam G. Li X, von Wachenfeldt K, Valfridsson C, Bullens S, Messaoudi I, Bader L, Cowan KJ, Kamath A, van Bruggen N, Bunting S, Frend?us B, Grove KL Molecular Metabolism, Available online 11 June 2013
medical_services Therapy IndicationsMarkers of inflammation and bone remodelling associated with improvement in clinical response measures in psoriatic arthritis patients treated with golimumab (2012) Wagner CL, Visvanathan S, Elashoff M, McInnes IB, Mease PJ, Krueger GG, Murphy FT, Papp K, Gomez-Reino JJ, Mack M, Beutler A, Gladman D, Kavanaugh A Ann Rheum Dis. 2012 Sep 12. [Epub ahead of print]
medical_services Therapy IndicationsHomozygous mutation in SAMHD1 gene causes cerebral vasculopathy and early onset stroke (2011) Xin B, Jones S, Puffenberger EG, Hinze C, Bright A, Tan H, Zhou A, Wu G, Vargus-Adams J, Agamanolis D, Wang H Proc Natl Acad Sci U S A. 2011 Mar 14. [Epub ahead of print]
medical_services Therapy IndicationsProteomic changes induced by anaesthesia and muscle relaxant treatment prior to electroconvulsive therapy (2011) Stelzhammer V, Rothermundt M, Guest PC, Michael N, Sondermann C, Kluge W, Martins-de-Souza D, Rahmoune H, Bahn S Proteomics Clin Appl. 2011 Oct 17.
medical_services Therapy IndicationsBiomarkers and Depressive Symptoms in a Sample of Cognitively Intact and Alzheimer?s Disease Elderly Males (2011) Hall JR, Vo HT, Johnson LA, Winter S, Barber RC, O?Bryant SE Neuroscience & Medicine, 2011, 2, 306-312
medical_services Therapy IndicationsEffects of Echinaforce? treatment on ex vivo-stimulated blood cells (2011) Ritchie MR, Gertsch J, Klein P, Schoop R Phytomedicine. 2011 Jul 15;18(10):826-31
medical_services Therapy IndicationsCox-2 expression, PGE2 and cytokines production are inhibited by endogenously synthesized n-3 PUFAs in inflamed colon of fat-1 mice (2011) Gravaghi C, La Perle KM, Ogrodwski P, Kang JX, Quimby F, Lipkin M, Lamprecht SA J Nutr Biochem. 2011 Apr;22(4):360-5
medical_services Therapy IndicationsIL-1RL2 and Its Ligands Contribute to the Cytokine Network in Psoriasis (2010) Blumberg H, Dinh H, Dean C Jr, Trueblood ES, Bailey K, Shows D, Bhagavathula N, Aslam MN, Varani J, Towne JE, Sims JE J Immunol 185:4354-62.
medical_services Therapy IndicationsMice lacking Tbk1 activity exhibit immune cell infiltrates in multiple tissues and increased susceptibility to LPS-induced lethality (2010) Marchlik E, Thakker P, Carlson T, Jiang Z, Ryan M, Marusic S, Goutagny N, Kuang W, Askew GR, Roberts V, Benoit S, Zhou T, Ling V, Pfeifer R, Stedman N, Fitzgerald KA, Lin LL, Hall JP J Leukoc Biol. 88: 1171-80.
medical_services Therapy IndicationsInsight in modulation of inflammation in response to diclofenac intervention: a human intervention study. (2010) van Erk MJ, Wopereis S, Rubingh C, van Vliet T, Verheij E, Cnubben NH, Pedersen TL, Newman JW, Smilde AK, van der Greef J, Hendriks HF, van Ommen B BMC Med Genomics 3: 5.
medical_services Therapy IndicationsBacteria challenge in smoke-exposed mice exacerbates inflammation and skews the inflammatory profile (2009) Gaschler GJ, Skrtic M, Zavitz CC, Lindahl M, Onnervik PO, Murphy TF, Sethi S, St?mpfli MR. Am J Respir Crit Care Med. 179: 666-75.
medical_services Therapy IndicationsRIP4 Regulates Epidermal Differentiation and Cutaneous Inflammation. (2009) Rountree RB, Willis CR, Dinh H, Blumberg H, Bailey K, Dean C Jr, Peschon JJ, Holland PM J Invest Dermatol 130: 102-112.
medical_services Therapy IndicationsVaccination with an Attenuated Strain of Francisella novicida Prevents T-Cell Depletion and Protects Mice Infected with the Wild-Type Strain from Severe Sepsis. (2009) Sharma J, Li Q, Mishra BB, Georges MJ, Teale JM Infect Immun 77: 4314-4326.
medical_services Therapy IndicationsAtorvastatin Restores Endothelial Function in Offspring of Protein-Restricted Rats in a Cholesterol-Independent Manner. (2009) Torrens C, Kelsall CJ, Hopkins LA, Anthony FW, Curzen NP, Hanson MA Hypertension 53: 661-667.
medical_services Therapy IndicationsThe involvement of pro-inflammatory cytokines in nephrogenic systemic fibrosis - a mechanistic hypothesis based on preclinical results from a rat model treated with gadodiamide. (2009) Steger-Hartmann T, Raschke M, Riefke B, Pietsch H, Sieber MA, Walter J Exp Toxicol Pathol 61: 537-552.
medical_services Therapy Indications"Host Tissue Damage" Signal ATP Impairs IL-12 and IFNgamma Secretion in LPS Stimulated Whole Human Blood. (2008) Nalos M, Huang S, Sluyter R, Khan A, Santner-Nanan B, Nanan R, McLean AS Intensive Care Med 34: 1891-1897.
medical_services Therapy IndicationsMCP-1-deficient mice show reduced neuroinflammatory responses and increased peripheral inflammatory responses to peripheral endotoxin insult. (2008) Thompson WL, Karpus WJ, Van Eldik LJ J Neuroinflammation 5: 35.
medical_services Therapy IndicationsDexamethasone inhibits high glucose-, TNF-alpha-, and IL-1beta-induced secretion of inflammatory and angiogenic mediators from retinal microvascular pericytes. (2008) Nehm? A, Edelman J Invest Ophthalmol Vis Sci 49: 2030-2038.
medical_services Therapy IndicationsTwo distinct activation states of plasmacytoid dendritic cells induced by influenza virus and CpG 1826 oligonucleotide. (2008) Iparraguirre A, Tobias JW, Hensley SE, Masek KS, Cavanagh LL, Rendl M, Hunter CA, Ertl HC, von Andrian UH, Weninger W J Leukoc Biol 83: 610-620.
medical_services Therapy IndicationsSirtuin regulates cigarette smoke-induced proinflammatory mediator release via RelA/p65 NF-kappaB in macrophages in vitro and in rat lungs in vivo: implications for chronic inflammation and aging. (2007) Yang SR, Wright J, Bauter M, Seweryniak K, Kode A, Rahman I Am J Physiol Lung Cell Mol Physiol 292: L567-L576.
medical_services Therapy IndicationsSignal transducer and activator of transcription 3 signaling within hepatocytes attenuates systemic inflammatory response and lethality in septic mice. (2007) Sakamori R, Takehara T, Ohnishi C, Tatsumi T, Ohkawa K, Takeda K, Akira S, Hayashi N Hepatology 46: 1564-1573.
medical_services Therapy IndicationsMultiplex proteomic approaches to sepsis research: case studies employing new technologies. (2005) Heuer JG, Cummins DJ, Edmonds BT Expert Rev Proteomics 2: 669-680.
medical_services Therapy IndicationsAdoptive transfer of in vitro-stimulated CD4+CD25+ regulatory T cells increases bacterial clearance and improves survival in polymicrobial sepsis. (2005) Heuer JG, Zhang T, Zhao J, Ding C, Cramer M, Justen KL, Vonderfecht SL, Na S J Immunol 174: 7141-7146.
medical_services Therapy IndicationsSimultaneous analysis of host and pathogen interactions during an in vivo infection reveals local induction of host acute phase response proteins, a novel bacterial stress response, and evidence of a host-imposed metal ion limited environment. (2004) Motley ST, Morrow BJ, Liu X, Dodge IL, Vitiello A, Ward CK, Shaw KJ Cell Microbiol 6: 849-865.
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