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TNF alpha antagonists

Athanasios Tragiannidis, Ioannis Kyriakidis, Ilse Zündorf, Andreas H Groll
Macromolecular immunosuppressive monoclonal antibodies and fusion proteins directed against molecules or cells involved in inflammation and immunity represent a recent and important addition to our therapeutic armamentarium. Tumor necrosis alpha (TNFα) is a cytokine involved in systemic inflammation and clinical utilization of its antagonists has revolutionized treatment of juvenile rheumatoid and psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, and plaque psoriasis. Clinical utility has also been demonstrated for use against steroid-refractory graft-vs-host disease and other immune-mediated conditions...
October 21, 2016: Mycoses
Ingunn Holen, Diane V Lefley, Sheila E Francis, Sarah Rennicks, Steven Bradbury, Robert E Coleman, Penelope Ottewell
BACKGROUND: We have recently identified interleukin 1B (IL-1B) as a potential biomarker for predicting breast cancer patients at increased risk for developing bone metastasis. In mouse models, IL-1B and its receptor (IL-1R1) are upregulated in breast cancer cells that metastasise to bone compared with cells that do not. We have now investigated the functional role of IL-1 by blocking IL-1R signalling with the clinically licensed antagonist, anakinra. METHODOLOGY: 6-week old female BALB/c mice received a subcutaneous or intra-venous injection of MDA-MB-231-IV or MCF7 cells...
September 27, 2016: Oncotarget
Bindu Madhavi Mudduluru, Shalin Shah, Steven Shamah, Arun Swaminath
Tumor necrosis factor alpha (TNF alpha) antagonists are biologic agents used in the management of inflammatory conditions such as rheumatoid arthritis, seronegative spondyloarthropathies and inflammatory bowel disease. These agents have been recently shown to cause a syndrome called anti-TNF induced lupus (ATIL), a rare condition which has similar clinical manifestations to idiopathic systemic lupus erythematosus (SLE). Given that extra-intestinal manifestations of inflammatory bowel disease include arthritis, it can be difficult to separate arthritis due to underlying disease from drug-induced arthritis...
October 17, 2016: Postgraduate Medicine
Semjon Seemann, Amelie Lupp
BACKGROUND: Chemokine receptor 4 (CXCR4) is a multifunctional G protein-coupled receptor that is activated by its natural ligand, C-X-C motif chemokine 12 (CXCL12). As a likely member of the lipopolysaccharide (LPS)-sensing complex, CXCR4 is involved in pro-inflammatory cytokine production and exhibits substantial chemo-attractive activity for various inflammatory cells. Here, we aimed to characterize the effects of CXCR4 blockade in systemic inflammation and to evaluate its impact on organ function...
October 3, 2016: Journal of Biomedical Science
Samah M Elaidy, Soha S Essawy
BACKGROUND: The most widespread chronic fibrosing lung disease is idiopathic pulmonary fibrosis. Lung serotonin (5-HT) content is increased during pulmonary fibrosis with the implication of 5-HT2 receptors in the pathogenesis. Serotonin plays important roles in alveolar macrophages function through 5-HT2C receptors activation. Numerous studies described the important role of 5-HT2A/B receptor blockers in suppressing different types of fibrosis as idiopathic pulmonary fibrosis. The current study pointed to examine the antifibrotic effects of RS-102221 and/or terguride through in vivo model of pulmonary fibrosis...
August 12, 2016: Pharmacological Reports: PR
Yehua Wang, Haibo Wang, Jian Jiang, Deyong Zhao, Yong Liu
BACKGROUND: Tumor necrosis factor α (TNFα) antagonists, namely, golimumab, adalimumab, infliximab, etanercept and certolizumab have been prescribed to alleviate and treat ankylosing spondylitis (AS). However, the lack of comparative evidence does not enable us to make constructive recommendations particularly for AS patient populations. METHODS: Eligible controlled trials regarding the above 5 anti-TNFα therapies were searched electronically through PubMed, Embase and Cochrane until April 1, 2015...
September 19, 2016: Cellular Physiology and Biochemistry
Zhaoqun Liu, Zhi Zhou, Lingling Wang, Limei Qiu, Huan Zhang, Hao Wang, Linsheng Song
We have now cloned an alpha-1 adrenergic receptor (A1AR) from the cDNA library of oyster Crassostrea gigas, designating as CgA1AR-1. The full length of CgA1AR-1 was 1149 bp and it encodes a protein of 382 amino acids containing a 7 transmembrane domain, whose putative topology was similar to the A1ARs in higher organisms and shared similarity of 19% with mammalian A1ARs according to the phylogenic analysis. After cell transfection of CgA1AR-1 into HEK293T cells and the incubation with its specific agonist norepinephrine (NE), the concentration of second messenger Ca(2+) increased significantly (p < 0...
September 12, 2016: Fish & Shellfish Immunology
B Hellmich
Imaging methods, such as joint and color duplex sonography, magnetic resonance imaging (MRI) and positron emission tomography (PET) nowadays facilitate the diagnosis of polymyalgia rheumatica and large vessel vasculitides and have now been included in the new classification criteria. In patients with typical symptoms, color duplex sonography of the temporal artery can replace a biopsy of the temporal artery for the diagnosis of giant cell arteritis (GCA); however, the role of these methods for patient follow-up and assessment of prognosis is unclear...
September 8, 2016: Der Internist
Doreen E Szollosi, Ola A M Ghoneim, Mohammed K Manzoor, Jyothi Dhuguru, Ivan O Edafiogho
Pro-inflammatory mediators including TNF-alpha, IL-6, and nitric oxide are important for the regulation of the immune response when an infection is present, but when overproduced, it can be responsible for the development of tissue and organ injury seen in sepsis, as well as severe asthma, and autoimmune diseases such as Crohn's disease and rheumatoid arthritis. Data from our lab to characterize the novel compound enaminone E121 have suggested that macrophages stimulated with lipopolysaccharide (LPS) release significantly decreased levels of TNF-alpha and IL-6 as measured by enzyme-linked immunosorbent assay as compared to the DMSO control group...
September 10, 2016: Inflammation
Hiroyuki Sumi, Masakazu Inazuka, Kentaro Hashimoto, Tomoyasu Ishikawa, Sei Yoshida, Masato Yabuki
Inhibitors of apoptosis proteins (IAPs) are a family of antiapoptotic regulators that have attracted attention as potential targets for cancer therapeutics. Although recent studies have revealed that small-molecule IAP antagonists induce tumor selective cell death in an autocrine tumor necrosis factor (TNF)α-dependent manner, the single-agent efficacy of IAP antagonists is restricted to a small subset of cancer cells. In this study, we showed that the single-agent activity of T-3256336 was limited to a few cancer cell lines in vitro, and these cell lines were defined by relatively high levels of TNFα mRNA expression...
October 14, 2016: Biochemical and Biophysical Research Communications
Lilian Gobbo Gabriele, Ana Carolina Morandini, Thiago José Dionísio, Carlos Ferreira Santos
BACKGROUND: The Renin-Angiotensin System (RAS) has been reported as an important modulator of inflammatory and immune responses. Evidence suggests an alternative Angiotensin (Ang) 1-7 / Mas receptor (Mas) axis as counter-regulatory to the classical RAS AngII / Angiotensin II type 1 (AT1) receptor axis. It is known that periodontal pathogens elicit host-derived immune response due to cytokines release such as interleukin (IL)-1β, and fibroblasts are among the most numerous sentinel cells that contribute to this production...
August 19, 2016: Journal of Periodontology
Ning-Ning Chen, Fuxin Wei, Le Wang, Shangbin Cui, Yong Wan, Shaoyu Liu
Tumor necrosis factor alpha (TNF-α) is an essential cytokine that mediates cell death and has been shown to play a potential role in inducing neural stem cell (NSC) apoptosis. We have previously shown that TNF-α antagonist etanercept can suppress the transplanted NSC apoptosis induced by TNF-α in spinal cord injury (SCI) sites; however, the precise molecular mechanism remains unclear. This study aimed to investigate the signaling pathways responsible for TNF-α-induced apoptosis in NSCs. TNF-α treatment impairs cell viability and increases apoptosis of NSCs in concentration- and time-dependent manners...
August 16, 2016: Neurochemical Research
Ji Yoon Lee, Seok-Ho Hong, Minsang Shin, Hye-Ryeon Heo, In Ho Jang
The metastatic spread of tumor cells via lymphatic vessels affects the relapse of tumor patients. New lymphatic vessel formation, including lymphangiogenesis, is promoted in the tumor environment. The lymphangiogenic factor VEGF-C can mediate lymphatic vessel formation and induce tumor metastasis by binding with FLT4. In melanoma, metastasis via lymphatics such as lymph nodes is one of the main predictors of poor outcome. Thus, we investigated whether blockade of FLT4 can reduce metastasis via the suppression of lymphatic capillaries...
September 16, 2016: Biochemical and Biophysical Research Communications
K Herberger
Pyoderma gangrenosum (PG) is an ulcerating, neutrophilic dermatosis of unknown etiology. Clinical appearance is characterized by sudden onset of sterile pustules that rapidly develop into very painful ulcerations with violaceous, undermined borders. Due to the lack of specific diagnostic and therapeutic markers, PG is a diagnosis of exclusion. An association with further diseases such as chronic inflammatory bowel disease, rheumatoid arthritis, diabetes, neoplasms, or metabolic syndrome exists in over 50 % of cases...
September 2016: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
(no author information available yet)
When PUVA therapy and immunosuppressants such as methotrexate are ineffective, TNF alpha antagonists are an option for patients with severe plaque psoriasis, in the absence of a better alternative. This is also the case for patients with psoriatic arthritis after failure of a "disease-modifying" antirheumatic drug. Apremilast, an oral immunosuppressant that inhibits phosphodiesterase type 4, has been authorised in the European Union for use in these settings. In patients with plaque psoriasis, oral apremilast was compared with subcutaneous etanercept, aTNF alpha antagonist, in a randomised, doubleblind, placebo-controlled trial lasting 16 weeks and involving 250 patients in whom other treatments had failed or were inappropriate...
June 2016: Prescrire International
F Boufidou, C Nikolaou
Mounting data of evidence that have emerged during the last twenty years, point towards the existence of an inflammatory mechanism underlying the pathophysiology of depressive disorder. These data have inspired a number of clinical studies characterized by the administration of inflammatory response altering medication in addition to conventional medication in depressive disorder patients. The drugs were either Non Steroid Anti-inflammatory Drugs (NSAIDs) or Tumor Necrosis Factor-alpha (TNFa) inhibitors and were selected among those that are already in use for various diseases related to the immune system...
April 2016: Psychiatrikē, Psychiatriki
Jorge Reyes-García, Edgar Flores-Soto, Héctor Solís-Chagoyán, Bettina Sommer, Verónica Díaz-Hernández, Luz María García-Hernández, Luis M Montaño
Tumor necrosis factor alpha (TNF-α) is a potent proinflammatory cytokine that plays a significant role in the pathogenesis of asthma by inducing hyperresponsiveness and airway remodeling. TNF-α diminishes the L-type voltage dependent Ca(2+) channel (L-VDCC) current in cardiac myocytes, an observation that seems paradoxical. In guinea pig sensitized tracheas KCl responses were lower than in control tissues. Serum from sensitized animals (Ser-S) induced the same phenomenon. In tracheal myocytes from nonsensitized (NS) and sensitized (S) guinea pigs, an L-VDCC current (ICa) was observed and diminished by Ser-S...
2016: Mediators of Inflammation
P Kleniewska, A Gorąca
: This study was designated to estimate protective role of ET(A) and ET(B) receptor antagonist against endothelin 1 (ET-1)-induced oxidative stress in lungs and determine whether these effects are mediated by nitric oxide (NO) synthase. Experiments were performed on Wistar rats divided into the following groups: I - saline (0.9% NaCl); II - ET-1 (3 microg/kg b. w.), III - BQ123 (1 mg/kg b. w.) + ET-1 (3 microg/kg b. w.), IV - BQ788 (3 mg/kg b. w.) + ET-1 (3 microg/kg b. w.), V - N-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg b...
July 15, 2016: Physiological Research
Eduardo Mulato do Vale, Cecília Coelho Xavier, Brenda Gomes Nogueira, Bruna Caldas Campos, Pedro Everson Alexandre de Aquino, Roberta Oliveira da Costa, Luzia Kalyne Almeida Moreira Leal, Silvânia Maria Mendes de Vasconcelos, Kelly Rose Tavares Neves, Glauce Socorro de Barros Viana
Ketamine (KET), a NMDA antagonist, exerts an antidepressant effect at subanaesthetic doses and possesses analgesic and anti-inflammatory activities. We evaluated the involvement of KET antinociceptive and anti-inflammatory effects with its antidepressant action. Male Swiss mice were subjected to formalin, carrageenan-induced paw oedema and forced swimming tests, for assessing antinociceptive, anti-inflammatory and antidepressant effects. The treatment groups were as follows: control, KET (2, 5 and 10 mg/kg), lithium (LI: 5 mg/kg) and KET2 + LI5 combination...
July 8, 2016: Basic & Clinical Pharmacology & Toxicology
Anastasia Atanasova Chokoeva, José Carlos Cardoso, Uwe Wollina, Georgi Tchernev
Pyoderma gangrenosum (PG) represents a rare skin disorder, with several clinical variants and still not fully understood ethiopathogenesis. Often associated with inflammatory or neoplastic disease, PG is nowadays considered an inflammatory neutrophilic disease with common underlying morbidity. Modern treatment options are oriented towards key mechanisms underlying the pathogenesis of the disease, namely inflammatory mediators, and seem to be the most effective treatment currently available. Although promising, the results are not invariable and these treatments are sometimes surrounded by controversy, as recent studies have reported cases that are refractory to therapy with biological agents...
July 5, 2016: Wiener Medizinische Wochenschrift
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