Multiple doses of intravenous interleukin 10 in steroid-refractory Crohn's disease

被引:422
作者
vanDeventer, SJH
Elson, CO
Fedorak, RN
机构
[1] UNIV ALABAMA,DIV GASTROENTEROL,BIRMINGHAM,AL 35294
[2] UNIV ALBERTA,DIV GASTROENTEROL,EDMONTON,AB,CANADA
关键词
D O I
10.1053/gast.1997.v113.pm9247454
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: Interleukin 10 (IL-10) is a cytokine with immunosuppressive and anti-inflammatory activities, Gene-targeted IL-10-deficient mice develop a chronic intestinal inflammatory disease that is reminiscent of Crohn's disease, The present double-blind randomized multicenter trial was designed to evaluate the safety, tolerance, and pharmacokinetics of IL-10 in Crohn's disease, Methods: Forty-six patients with active steroid-resistant Crohn's disease were treated with one of five doses of recombinant human IL-10 (0.5, 1, 5, 10, or 25 mu g/kg) or placebo administered once daily by intravenous bolus injection over 7 consecutive days, Results: Treatment was safe and well tolerated, and no evidence for IL-10 accumulation was observed at the end of the treatment period, At the end of the study, Crohn's disease activity scores were 179 in IL-10-treated patients and 226 in patients receiving placebo. The proportion of patients that experienced a complete remission at any time in the 3-week follow-up period was 50% in the IL-10 group and 23% in placebo-treated patients, Conclusions: These results indicate that IL-10 administered as a daily bolus injection over 1 week is safe and well tolerated and may be clinically efficacious.
引用
收藏
页码:383 / 389
页数:7
相关论文
共 22 条
  • [1] INTERLEUKIN-10 (IL-10) INHIBITS THE RELEASE OF PROINFLAMMATORY CYTOKINES FROM HUMAN POLYMORPHONUCLEAR LEUKOCYTES - EVIDENCE FOR AN AUTOCRINE ROLE OF TUMOR-NECROSIS-FACTOR AND IL-1-BETA IN MEDIATING THE PRODUCTION OF IL-8 TRIGGERED BY LIPOPOLYSACCHARIDE
    CASSATELLA, MA
    MEDA, L
    BONORA, S
    CESKA, M
    CONSTANTIN, G
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 178 (06) : 2207 - 2211
  • [2] INTERLEUKIN-10 (IL-10) UP-REGULATES IL-1 RECEPTOR ANTAGONIST PRODUCTION FROM LIPOPOLYSACCHARIDE-STIMULATED HUMAN POLYMORPHONUCLEAR LEUKOCYTES BY DELAYING MESSENGER-RNA DEGRADATION
    CASSATELLA, MA
    MEDA, L
    GASPERINI, S
    CALZETTI, F
    BONORA, S
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 179 (05) : 1695 - 1699
  • [3] CORRELATIONS BETWEEN CLINICAL ACTIVITY, ENDOSCOPIC SEVERITY, AND BIOLOGICAL PARAMETERS IN COLONIC OR ILEOCOLONIC CROHNS-DISEASE - A PROSPECTIVE MULTICENTER STUDY OF 121 CASES
    CELLIER, C
    SAHMOUD, T
    FROGUEL, E
    ADENIS, A
    BELAICHE, J
    BRETAGNE, JF
    FLORENT, C
    BOUVRY, M
    MARY, JY
    MODIGLIANI, R
    COLOMBEL, JF
    CORTOT, A
    LESCUT, D
    BITOUN, A
    LEMANN, M
    SALMERON, M
    THEROND, JP
    VERNISSE, B
    SEE, A
    RAOUL, JL
    [J]. GUT, 1994, 35 (02) : 231 - 235
  • [4] CHERNOFF AE, 1995, J IMMUNOL, V154, P5492
  • [5] Tolerance towards resident intestinal flora in mice is abrogated in experimental colitis and restored by treatment with interleukin-10 or antibodies to interleukin-12
    Duchmann, R
    Schmitt, E
    Knolle, P
    zumBuschenfelde, KHM
    Neurath, M
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1996, 26 (04) : 934 - 938
  • [6] FIORENTINO DF, 1991, J IMMUNOL, V147, P3815
  • [7] Grool TA, 1996, GASTROENTEROLOGY, V110, pA918
  • [8] Interleukin-10 induces a long-term antigen-specific anergic state in human CD4(+) T cells
    Groux, H
    Bigler, M
    deVries, JE
    Roncarolo, MG
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (01) : 19 - 29
  • [9] Pharmacokinetics and immunomodulatory properties of intravenously administered recombinant human interleukin-10 in healthy volunteers
    Huhn, RD
    Radwanski, E
    OConnell, SM
    Sturgill, MG
    Clarke, L
    Cody, RP
    Affrime, MB
    Cutler, DL
    [J]. BLOOD, 1996, 87 (02) : 699 - 705
  • [10] KASAMA T, 1994, J IMMUNOL, V152, P3559