Tumour necrosis factor alpha as a therapeutic target for immune-mediated inflammatory diseases.
ABSTRACT Preclinical studies have identified and validated tumour necrosis factor alpha (TNFalpha) as a key disease molecule and therapeutic target for immunotherapeutic intervention in many immune-mediated inflammatory diseases. Clinical indications include rheumatoid arthritis, Crohn's disease, ankylosing spondylitis and psoriasis. Recent clinical findings indicate that many chronic inflammatory disorders share certain pathogenic pathways, whereas others are limited to particular disease phenotypes. Better understanding of these pathogenic pathways will inform the development of new therapeutic approaches leading to more complete and sustained disease remissions.
Article: Infliximab for chronic obstructive pulmonary disease: towards a more specific inflammation targeting?VAN DER VAART H, KOETER GH, POSTMA DS, KAUFFMAN HF, TEN HACKEN NH: First study of infliximab treatment in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. (2005) 172(4):465-469.[Show abstract] [Hide abstract]
ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a predominantly smoking-related condition in which chronic progressive airways obstruction results because of inflammation that is triggered and maintained by the causative agent and enhanced during exacerbations. Inflammation is dominated by neutrophils, and macrophages and their mediators. TNF-α is a proinflammatory cytokine involved in COPD pathogenesis. Treatment of the stable disease is mainly inhalatory with anticholinergics, β2 agonsists and inhaled corticosteroids being involved in various stages of the disease. Novel therapeutic agents are currently under investigation for COPD treatment and some of them target various inflammation mediators. Infliximab is a monoclonal anti-TNF-α antibody with demonstrated efficacy in other autoimmune diseases, such as Crohn’s disease and rheumatoid arthritis. The current study assesses the scientific rationale for the use of infliximab in COPD patients.Expert Opinion on Investigational Drugs 01/2006; 15(2). DOI:10.1517/135437126.96.36.199 · 5.43 Impact Factor
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ABSTRACT: 3-Alkyl-2-aryl-2-cyclopenten-1-one oxime derivatives (1) were studied as a novel class of inhibitors of tumor necrosis factor α (TNF-α) with regard to synthesis and in vitro SAR inhibition of TNF-α. The in vitro IC50 values of these compounds in rat and human peripheral blood mononuclear cells were at the sub-micromolar level.Bioorganic & medicinal chemistry letters 05/2014; 24(13). DOI:10.1016/j.bmcl.2014.04.115 · 2.33 Impact Factor
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ABSTRACT: Objectives : Hwangnyeonhaedok-tang (Huanglian Jiedu Tang; HHT) has been widely used for purging' 'fire' and lessening virulence of any pathogenic organism. However it has been rarely conducted to evaluate the immuno-biological activity. In this study, we evaluated anti-inflammatory effects of HHT in LPS-activated Raw264.7 cells. Methods : Cells were treated with of LPS 1 h prior to the addition of HHT. Cell viability was measured by MTT assay. The production of NO was determined by reacting cultured medium with Griess reagent. PGE2 and proinflammatory cytokines were detected by ELISA. Expression of iNOS, COX-2, and NF- were analyzed by immunoblot analysis. Results : All three doses of HHT (0.03, 0.10 and 0.30 mg/ml) had no significant cytotoxicity during the entire experimental period. The levels of NO and PGE2 were dramatically augmented by LPS compared to control. However, HHT extract dose-dependently reduced these increases. Expression of iNOS and COX-2 protein were also decreased by treatment with HHT extract. Furthermore, HHT extract significantly reduced the nuclear translocation of NF- which is critical in regulating inflammation through transcription of iNOS and COX-2. In addition, HHT extract reduced the elevated production of inflammatory cytokines including TNF-, IL- and IL-6. Conclusions : The results in this study demonstrate that HHT extract exerts anti-inflammatory activities through the inhibition of NO, PGE2 and proinflammatory cytokines production via the suppression of NF-.01/2009; 24(4).