Investigational cytokine-targeted therapies for ulcerative colitis

被引:6
作者
Monteleone, Giovanni [1 ]
Pallone, Francesco [1 ]
Caprioli, Flavio [2 ,3 ]
机构
[1] Univ Roma Tor Vergata, Dept Syst Med, I-00133 Rome, Italy
[2] Univ Milan, Dept Pathophysiol & Transplantat, I-20122 Milan, Italy
[3] Osped Policlin Milano, Fdn IRCCS Ca Granda, Unit Gastroenterol 2, I-20122 Milan, Italy
关键词
CD4+T cells; cytokines; inflammatory bowel diseases; intestinal inflammation; TUMOR-NECROSIS-FACTOR; CHRONIC INTESTINAL INFLAMMATION; REGULATORY T-CELLS; FACTOR-ALPHA; INTERFERON-GAMMA; MONOCLONAL-ANTIBODY; DOUBLE-BLIND; RHEUMATOID-ARTHRITIS; OXAZOLONE COLITIS; BOWEL-DISEASE;
D O I
10.1517/13543784.2013.813931
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Introduction: Up to one-third of patients with ulcerative colitis (UC) do not respond to standard medications, including mesalamine, steroids and thio-purines. The recognition that UC-related pathological process is the result of an altered balance between inflammatory and counter-regulatory signals, mostly mediated by cytokines, has led to the development of novel compounds, which are now ready to move into clinical practice. This article summarizes the recent data on the development and use of compounds either inhibiting inflammatory cytokines or enhancing the activity of counter-regulatory cytokines in patients with UC and murine models of UC. Areas covered: A PubMed search was performed using the following keywords: 'ulcerative colitis', 'therapy', 'treatment' and 'cytokine'. In addition, ongoing clinical trials were checked and compounds were searched on the website of pharmaceutical companies. Expert opinion: Several investigational cytokine-based therapies have provided promising results in attenuating clinical activity in patients with UC and mice with experimental colitis. However, clinical and immunological heterogeneity of UC patients, therapy-related side effects and redundant biological functions of cytokines represent potential pitfalls and should be considered in optimizing therapeutic strategies.
引用
收藏
页码:1123 / 1132
页数:10
相关论文
共 94 条
[1]
The interleukin-23 axis in intestinal inflammation [J].
Ahern, Philip P. ;
Izcue, Ana ;
Maloy, Kevin J. ;
Powrie, Fiona .
IMMUNOLOGICAL REVIEWS, 2008, 226 :147-159
[2]
Differences in binding and effector functions between classes of TNF antagonists [J].
Arora, Taruna ;
Padaki, Rupa ;
Liu, Ling ;
Hamburger, Agnes E. ;
Ellison, Aaron R. ;
Stevens, Seth R. ;
Louie, James S. ;
Kohno, Tadahiko .
CYTOKINE, 2009, 45 (02) :124-131
[3]
Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease [J].
Baert, F ;
Noman, M ;
Vermeire, S ;
Van Assche, G ;
D'Haens, G ;
Carbonez, A ;
Rutgeerts, P .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (07) :601-608
[4]
Baumann H, 1996, J IMMUNOL, V157, P284
[5]
The tumor necrosis factor ligand and receptor families [J].
Bazzoni, F ;
Beutler, B .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 334 (26) :1717-1725
[6]
A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells [J].
Black, RA ;
Rauch, CT ;
Kozlosky, CJ ;
Peschon, JJ ;
Slack, JL ;
Wolfson, MF ;
Castner, BJ ;
Stocking, KL ;
Reddy, P ;
Srinivasan, S ;
Nelson, N ;
Boiani, N ;
Schooley, KA ;
Gerhart, M ;
Davis, R ;
Fitzner, JN ;
Johnson, RS ;
Paxton, RJ ;
March, CJ ;
Cerretti, DP .
NATURE, 1997, 385 (6618) :729-733
[7]
Oxazolone colitis: A murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4 [J].
Boirivant, M ;
Fuss, IJ ;
Chu, A ;
Strober, W .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (10) :1929-1939
[8]
Inhibition of Smad7 with a specific antisense oligonucleotide facilitates TGF-β1-mediated suppression of colitis [J].
Boirivant, Monica ;
Pallone, Francesco ;
Di Giacinto, Claudia ;
Fina, Daniele ;
Monteleone, Ivan ;
Marinaro, Mariarosaria ;
Caruso, Roberta ;
Colantoni, Alfredo ;
Palmieri, Giampiero ;
Sanchez, Massimo ;
Strober, Warren ;
MacDonald, Thomas T. ;
Monteleone, Giovanni .
GASTROENTEROLOGY, 2006, 131 (06) :1786-1798
[9]
Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies - Systematic review and meta-analysis of rare harmful effects in randomized controlled trials [J].
Bongartz, T ;
Sutton, AJ ;
Sweeting, MJ ;
Buchan, I ;
Matteson, EL ;
Montori, V .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2006, 295 (19) :2275-2285
[10]
Interferon-beta(1b) treatment decreases tumor necrosis factor-alpha and increases interleukin-6 production in multiple sclerosis [J].
Brod, SA ;
Marshall, GD ;
Henninger, EM ;
Sriram, S ;
Khan, M ;
Wolinsky, JS .
NEUROLOGY, 1996, 46 (06) :1633-1638