) ;, UC, ( azathiop rine, Keywords Inflammatory bowel disease, refractory. , 34% 45% ( ulcerative colitis, 80% flammatory bowel disease, IBD ) IBD IBD

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1 (2007) , IBD IBD 1 IBD, R5 A :, E2mail: kaicwu@ fmmu1edu1cn, ,, Keywords Inflammatory bowel disease, refractory, 34% 45% ( ulcerative colitis, UC) 43% 56% (Crohnπs disease, CD) 80% CD UC, ( in2 flammatory bowel disease, IBD ) IBD, 30% CD 50% UC 1, IBD PubMed steroid2resistant ( ) / steroid2dependent ( ) / steroid2refractory( ) IBD 2006 ( ECCO) CD ( cortico2 steroid2dependent)( corticosteroid2 refractory) CD, IBD IBD, IBD : UC : ; ( ) ;, CD ;, ; UC,, UC ( azathiop rine, AZA) 62 (62MP),,, [ 1-2 ] CD, CD ( : ) CT ECCO, CD,, CD 2 IBD 211 AZA 62 MP, AZA 62MP 2 62 ( 62TGN ) 62 TGN DNA RNA, T AZA 62MP IBD, IBD B rooke [ 3 ] 1969 AZA CD,, CD AZA mg/ ( kg d) CD UC, AZA mg/ ( kg d) 6, UC AZA AZAUC 62MP UC CD Adler [ 4 ] 18

2 , 62MP 4, 48% UC, 13%, 62MP UC 61% Colona [ 5 ], 62MP CD,, AZA 62MP mg/ ( kg d ) mg/ ( kg d) AZA 62MP : AZA 62MP 50 mg/d, mg mg/ ( kg d ) mg/ ( kg d) AZA 62MP, 2 3, AZA 62 MP :, AZA 62MP IBD 113% 313%, ( thiopurine methyltransferase, TPMT) AZA 62MP, AZA 62MP TPMT TPMT, TPMT, TPMT 212 (methotrexate,mtx),,,,, DNA MTX 10, MTX IBD MTX,,MTX, MTX IBD,MTX CD,MTX IBD 5 3MTX CD, MTX 1MTX CD AZA,MTX CD,MTX 70% MTX UC 42, AZA, MTX ( 20 mg, ) 42%, 38% 6 MTX IBD MTX,MTX IBD AZA 62MP MTX mg, MTX IBD,, 25 mg MTX :, MTX, MTX, MTX, MTX IBD : (1) MTX CD, (2) MTX CD, mg,, ( 3 ) MTX 25 mg, 16 CD (4)MTX UC (5) MTX (6) MTX IBD (7) MTX [ 6 ] 213 ( cyclosporine), ( calcineurin), T IgE G 0 G 1 T Th, IL22 T ( TCGF) UC mg/ ( kg d), UC 80%, UC 31, 22 (4 18 ), 7114% 9114%, 1992,, Sandborn [ 7 ] , UC 68%, 42% UC AZA 62MP CD UC CD CD, 10 AZA /62MP CD, 9 Egan [ 8 ] CD, 90%, 82% CD AZA 62MP, AZA 62MP

3 1420 CD 4 mg/ ( kg d) 2 mg/ ( kg d ) 2 mg/ ( kg d) 4 mg/ ( kg d), 2 UC : (1) UC,, UC ; UC 2 4 mg/ ( kg d), UC (2) ( 3) UC, ( 2, 2 ) AZA 62MP ; AZA 62MP (4) UC, AZA 62MP (5) CD, [ 716 mg/ ( kg d) ] CD (6) CD,, AZA 62MP [ 6 ] : ;, ;, 214 ( Tacrolimus), 100,, T, IL22 TNF2 IFN2 ;, T, IL210 TGF2, ( inos),, UC CD 20,, CD, 67%, 15%, 1715% ; UC 53%, 2015%, 2615% UC CD,, UC CD, ( AZA 62MP ) CD CD,, CD, 4 CD, UC CD mg/ ( kg d) mg/ ( kg d),, 2,, IBD g/l, UC CD CD : 215 ( infliximab, IFX) IFX IBD CD, 1998 FDA IFX IgG1, 25%, TNF ( antibody dependent cell mediated cytotoxicity, ADCC),, IFX CD, CD ; UC, IFX UC, UC, IFX, IFX : (1) IFX ( AZA /62MP MTX) CD UC CD, IFX (2) IBD IFX 5 mg/kg, 2 h, 0, 2, 6 1 ; IFX 8 1,, 3 IFX; CD 10 mg/kg IFX,, 1 h, (3) IFX, ( 4) IFX IFX (5) IFX, [ 6 ] 216, IBD (mycophenolate mofetil,mmf) MMF ( inosine monophosphate dehydrogenase, IMP) MMF IMP, T B, MMF AZA /62MP

4 IBD MMF IBD, MMF IBD,, MMF,, MMF IBD ( thalidom ide, ) 20 50,, 1961 H IV IBD, TNF2 IL212,, LPS NF2 B IBD, IBD IBD, IBD,, :,,, UC CD, 3 IBD 311 IBD IBD, UC,, ; CD, CD, CD, 312 ( absorp tive leukocytaph2 eresis) TNF2 IL21 IL26 IL28 IBD IBD ( ),, IBD IBD, IBD,, UC, CD ( granocyte monocyte absorp tive aphere2 sis, GMA) UC, UC,,,, CD Matsui [ 9 ] GMA 7 CD, 5 GMA CD 52% 70%, CD, GMA CD GMA IBD60 m in 1, 5 GMA IBD,,, GMA IBD GMA, ( hematopoietic cell transp lantation, HCT) IBD, IBD NOD2 /CARD15 CD Baron [ 10 ] 1 CD CD NOD2 / CARD CD, IBD, IBD UC CD 14, 14 CD, CD, 7 [ 11 ] CD 19, ( IFX), 14 CD , 2, CD CD, IBD UC IBD IBD UC CD CD

5 1422 UC, IFX, CD MTX MMF, CD [ 1 ] Sohi S, Cohen RD. Management of refractory ulcerative colitis[ J ]. Curr Treat Op tions Gastroenterol, 2006, 9 (3) : [ 2 ] M ichetti P,Mottet C, Juillerat P, et al. Severe and steroid - resist2 ant Crohnπs disease[ J ]. D igestion, 2005, 71 (1) : [ 3 ] B rooke BN, Hoffmann DC, Swarbrick ET. Azathioprine for Crohnπs disease[ J ]. Lancet, 1969, 2 (7621) : [ 4 ] Adler DJ, Korelitz B I. The therapeutic efficacy of 62mercaptopurine in refractory ulcerative colitis [ J ]. Am J Gastroenterol, 1990, 85 (6) : [ 5 ] Colona T, Korelitz B I. The role of leukopenia in the 62mercap topu2 rine2induced rem ission of refractory Crohnπs disease [ J ]. Am J Gastroenterol, 1994, 89 (3) : [ 6 ] L ichtenstein GR, Abren MT, Coher R, et al. American gastroenter2 ological association institute technical review on corticosteroids, immunomodulators, and infliximabin inflammatory bowel disease [ J ]. Gastroenterology, 2006, 130 (3) : [ 7 ] SandbornW. A critical review of cyclosporine therapy in inflamma2 tory bowel disease[ J ]. Inflamm Bowel D is, 1995, 1: [ 8 ] Egan LJ, Sandborn WJ, Tremaine WJ. Clinical outcome following treatment of refractory inflammatory and fistulizing Crohnπs disease with intravenous cyclosporine [ J ]. Am J Gastroenterol, 1998, 93 (3) : [ 9 ] Matsui T, N ishimura T, Matake H, et al. Granulocytapheresis for Crohnπs disease: a report on seven refractory patients. [ J ]. Am J Gastroenterol, 2003, 98 (2) : [ 10 ] Baron FA, Hermanne JP, Dowlati A, et al. B ronchiolitis obliterans organizing pneumonia and ulcerative colitis after allogeneic bone marrow transplantation [ J ]. Bone Marrow Transplant, 1998, 21 (9) : [ 11 ] Leung Y, GeddesM, Storek J, et al. Hematopoietic cell transplan2 tation for Crohnπs disease; is it time? [ J ]. World J Gastroenterol, 2006, 12 (41) : : (2007) R5 A, Tufts,, 1,, ; ; Keywords Inflammatory bowel disease; Salieylic acids; Am inosalicylates ( am inosalicylates) ( in2 flammatory bowel disease, IBD) 50, 20 40, Nana Svartz Karolinska ( ) (52, 52am inosalicylic acid, 52ASA ) ( salicylazosulfapyridine, SASP),, ( ),, IBD, [ 1-2 ], ( ),, - IBD, SASP IBD [ 3 ] SASP SASP,, :, E2mail: zhengjj2218@1631com

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