Quantitive Cytokine mRNA Expression Profiles in the Colonic Mucosa of Patients with Steroid Naive Ulcerative Colitis During Active and Quiescent Disease

被引:78
作者
Matsuda, Reikei [1 ]
Koide, Tomoko [2 ]
Tokoro, Chikako [2 ]
Yamamoto, Tsuyoshi [1 ]
Godai, Ten'i [4 ]
Morohashi, Taiki [3 ]
Fujito, Yuji [1 ]
Takahashi, Daisuke [1 ]
Kawana, Ichiro [2 ]
Suzuki, Shinichiro [4 ]
Umemuro, Satoshi [5 ]
机构
[1] Fujisawa Shounandai Hosp, Dept Internal Med, Fujisawa, Kanagawa 2520802, Japan
[2] Yokohama City Univ, Dept Gastroenterol, Yokohama, Kanagawa 232, Japan
[3] Omori Red Cross Hosp, Dept Gastroenterol, Ohta Ku, Tokyo, Japan
[4] Fujisawa Shounandai Hosp, Dept Surg, Fujisawa, Kanagawa 2520802, Japan
[5] Yokohama City Univ, Grad Sch Med, Dept Med Sci & Cardiorenal Med, Yokohama, Kanagawa 232, Japan
关键词
ulcerative colitis; steroid naive patients; inflammatory cytokines; interleukin-8; real time PCR; inflammatory mucosa; INFLAMMATORY-BOWEL-DISEASE; PROINFLAMMATORY CD14(+)CD16(+)DR(++) MONOCYTES; SELECTIVE LEUKOCYTE APHERESIS; GRANULOCYTE/MONOCYTE APHERESIS; ADSORPTION APHERESIS; CLINICAL-RESPONSE; IMMUNE-SYSTEM; THERAPY; LEUKOCYTAPHERESIS; PREDNISOLONE;
D O I
10.1002/ibd.20759
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: Cytokines have validated roles in the immunopathogenesis of inflammatory bowel disease (IBD). This study was to investigate the expressions of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6. IL-8, and IL-10 mRNAs in the colonic mucosa of patients With ulcerative colitis (UC) during active and quiescent UC. Methods: At colonoscopy, biopsies were taken from inflamed and non-inflamed mucosa of patients with steroid-naive UC (n = 15), non-IBD inflammatory colitis controls (ICC, n = 6), and non-colitis controls (NCC, n = 14). The presence of extensive mononuclear cells and neutrophils infiltrate in the lamina propria, cryptitis, and epithelial damage defined an inflammatory lesion in the mucosa. Quantitative cytokine mRNA expressions in biopsies were measured by real-time polymerase chain reaction (PCR). Results: Of 15 UC patients, 3 remitted with 5-aminosalicylate and 11 received granulocytapheresis of these, 10 remitted. At baseline, IL-6, IL-8, TNF-alpha, and IL-10 mRNAs were high in inflamed mucosa compared with NCC (P < 0.01). In active UC, IL-6, IL-8 and IL-10 mRNAs were high compared with non-inflamed mucosa (P = 0.03, P = 0.03, P < 0.05, respectively). Both TNF-alpha mRNA (P = 0.03) and IL-6 mRNA (P = 0.04) were higher in UC compared with ICC. Even in non-inflamed mucosa. IL-8 and TNF-alpha mRNA expressions were high compared with NCC. Both IL-6 and IL-8 mRNAs decreased to normal levels after granulocytapheresis. Conclusions: During active UC, all 4 cytokine mRNA levels were high; only IL-6 and IL-8 mRNAs decreased to normal levels during remission. IL-8 mRNA was high even at sites of endoscopically quiescent UC during active disease. Steroid naive patients respond well to granulocytapheresis.
引用
收藏
页码:328 / 334
页数:7
相关论文
共 54 条
[1]   Selective leukocyte apheresis for the treatment of inflammatory bowel disease [J].
Abreu, Maria T. ;
Plevy, Scott ;
Sands, Bruce E. ;
Weinstein, Robert .
JOURNAL OF CLINICAL GASTROENTEROLOGY, 2007, 41 (10) :874-888
[2]  
ALLISON MC, 1998, INFLAMM BOWEL DIS, P9
[3]   The proinflammatory CD14+CD16+DR++ monocytes are a major source of TNF [J].
Belge, KU ;
Dayyani, F ;
Horelt, A ;
Siedlar, M ;
Frankenberger, M ;
Frankenberger, B ;
Espevik, T ;
Ziegler-Heitbrock, L .
JOURNAL OF IMMUNOLOGY, 2002, 168 (07) :3536-3542
[4]   Neutrophil apoptosis is delayed in patients with inflammatory bowel disease [J].
Brannigan, AE ;
O'Connell, PR ;
Hurley, H ;
O'Neill, A ;
Brady, HR ;
Fitzpatrick, JM ;
Watson, RWG .
SHOCK, 2000, 13 (05) :361-366
[5]   Treatment of patients with acute ulcerative colitis: Conventional corticosteroid therapy (MP) versus granulocytapheresis (GMA): A pilot study [J].
Bresci, G. ;
Parisi, G. ;
Mazzoni, A. ;
Scatena, F. ;
Capria, A. .
DIGESTIVE AND LIVER DISEASE, 2007, 39 (05) :430-434
[6]   Granulocyteaphaeresis in steroid-dependent inflammatory bowel disease:: a prospective, open, pilot study [J].
Domènech, E ;
Hinojosa, J ;
Esteve-Comas, M ;
Gomollón, F ;
Herrera, JM ;
Bastida, G ;
Obrador, A ;
Ruiz, R ;
Saro, C ;
Gassull, MA .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2004, 20 (11-12) :1347-1352
[7]  
Duchmann R, 1995, CLIN EXP IMMUNOL, V102, P448
[8]   Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn's disease [J].
Fedorak, RN ;
Gangl, A ;
Elson, CO ;
Rutgeerts, P ;
Schreiber, S ;
Wild, G ;
Hanauer, SB ;
Kilian, A ;
Cohard, M ;
LeBeaut, A ;
Feagan, B .
GASTROENTEROLOGY, 2000, 119 (06) :1473-1482
[9]   Interleukin-1 receptor antagonist as therapy for inflammatory disorders [J].
Freeman, BD ;
Buchman, TG .
EXPERT OPINION ON BIOLOGICAL THERAPY, 2001, 1 (02) :301-308
[10]   Treatment of active steroid-refractory inflammatory bowel diseases with granulocytapheresis: Our experience with a prospective study [J].
Giampaolo, Bresci ;
Giuseppe, Parisi ;
Michele, Bertoni ;
Alessandro, Mazzoni ;
Fabrizio, Scatena ;
Alfonso, Capria .
WORLD JOURNAL OF GASTROENTEROLOGY, 2006, 12 (14) :2201-2204