Alimentary TractSafety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease☆,☆☆,★
Section snippets
Patients
Eligible patients were adults with chronic active CD. Chronic active CD was defined by (1) a previous diagnosis of CD as documented by clinical, endoscopic, or histologic findings; (2) inflammation involving the colon, ileum, and colon or endoscopically evaluable disease of the ileum only, with or without external fistulas; and (3) a CDAI score during the week before inclusion into the study between 200 and 400 points despite treatment with systemic glucocorticoids for at least 3 months, with
Study population
A total of 412 patients were screened for inclusion at 43 centers. Eighty-three patients were excluded in the screening phase for the following reasons: insufficient activity or documentation of disease (n = 30), subject's decision to withdraw consent during screening (n = 15), excessive disease activity (n = 11), unacceptable concomitant medication (n = 9), abnormal laboratory test results (n = 8), history of cancer (n = 4), hepatitis B or C infection (n = 3), detection of signs of C. difficile
Discussion
Subcutaneous administration of rhuIL-10 in doses of 1, 4, or 8 μg/kg body wt for 28 consecutive days has been shown to be safe and well tolerated in patients with chronic active CD. The excellent patient compliance reflects both the good local and systemic tolerance to rhuIL-10. Adverse events frequently reported with rhuIL-10 (which cumulate in the 20-μg/kg dose group) include mild-to-moderate headache, fever, back pain, and dizziness. Moderate decreases in hemoglobin concentrations and
Acknowledgements
The authors thank Ulrich Meinzer for contribution in the preparation of samples, conduction of in vitro experiments, and handling of experimental data for the NF-κB work.
References (42)
- et al.
Cytokine mRNA profiles in inflammatory bowel disease mucosa detected by PCR amplification
Gastroenterology
(1992) - et al.
National cooperative Crohn's disease study: results of drug treatment
Gastroenterology
(1979) - et al.
European cooperative Crohn's disease study (ECCDS): results of drug treatment
Gastroenterology
(1984) - et al.
Immunoregulatory role of interleukin 10 in patients with inflammatory bowel disease
Gastroenterology
(1995) - et al.
IL-10 as a therapeutic strategy in the treatment of rheumatoid arthritis
Rheum Dis Clin North Am
(1998) - et al.
Interleukin (IL)-10 inhibits nuclear factor kappa B (NF kappa B) activation in human monocytes. IL-10 and IL-4 suppress cytokine synthesis by different mechanisms
J Biol Chem
(1995) - et al.
Interleukin-10–deficient mice develop chronic enterocolitis
Cell
(1993) - et al.
Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn's disease
Gastroenterology
(2000) - et al.
Multiple doses of intravenous interleukin 10 in patients with inflammatory bowel disease
Gastroenterology
(1997) - et al.
Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study
Gastroenterology
(1976)
Mechanisms in failure of infliximab in Crohn's disease
Lancet
Appearance of nuclear protease after embryonal carcicomal cells undergo differentiation
Dev Biol
Protein measurements with the Folin phenol reagent
J Biol Chem
A new measure of health status for clinical trials in inflammatory bowel disease
Gastroenterology
Randomised controlled trial of CDP571 antibody to tumour necrosis factor–alpha in Crohn's disease
Lancet
Interleukin-10 signaling blocks inhibitor of κB kinase activity and nuclear factor κB DNA binding
J Biol Chem
Enhanced production of interleukin 1-β by mononuclear cells isolated from mucosa with active ulcerative colitis or Crohn's disease
Gut
Tumour necrosis factor-alpha and interferon-gamma production measured at the single cell level in normal and inflamed human intestine
Clin Exp Immunol
Tumor necrosis factor-α, interleukin-1β and interleukin 6 expression in inflammatory bowel disease
Dig Dis Sci
Enhanced secretion of tumor necrosis factor-alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn's disease
Clin Exp Immunol
Development and validation of an endoscopic index of the severity for Crohn's disease: a prospective, multicentre study
Gut
Cited by (440)
Recent advances on emerging nanomaterials for diagnosis and treatment of inflammatory bowel disease
2023, Journal of Controlled ReleaseOral delivery of a functional algal-expressed TGF-β mimic halts colitis in a murine DSS model
2021, Journal of BiotechnologyThe Production and Function of Endogenous Interleukin-10 in Intestinal Epithelial Cells and Gut Homeostasis
2021, Cellular and Molecular Gastroenterology and HepatologyCELL THERAPY IN INFLAMMATORY BOWEL DISEASE
2021, Pharmacological Research
- ☆
Address requests for reprints to: Stefan Schreiber, M.D., First Medical Department, Christian-Albrechts-University, Schittenhelmstrasse 12, 24105 Kiel, Germany. e-mail: [email protected]; fax: (49) 431-597-1302.
- ☆☆
Supported by a grant from Schering-Plough Research Institute (Kenilworth, NJ). The fellowship of Dr. Nikolaus and the laboratory work were supported by additional grants from Mucosa immunologie gemeinnützige Forschungsgesellschaft mbH (MFG), a training and mobility of researchers program of the European Commission (ERB-4061-PL-97-0389), and by DFG SFB 415.
- ★
The Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group consists of the following centers. The number of patients enrolled at each center is given in parentheses: S. Schreiber (27), R. N. Fedorak (25), O. H. Nielsen (20), G. Wild (18), N. C. Williams (17), M. Jacyna (12), B. A. Lashner (11), P. Rutgeerts (10), A. Gangl (10), K. Isaacs (10), M. Gregor (9), E. J. Bernard (9), J. C. Koningsberger (8), C. Bernstein (8), A. H. Steinhart (8), C. Elson (7), S. Targan (7), S. J. H. van Deventer (7), J. Irvine (7), L. R. Da Costa (7), B. Feagan (7), S. Hanauer (6), L. F. Mayer (6), S. Katz (6), R. Befrits (6), J. Schölmerich (6), L. Abreu (6), M. A. Bigard (6), C. Sninsky (5), H. Tilg (5), P. Pare (5), W. J. Tremaine (4), B. Sands (4), B. Duclos (4), S. Chaussade (4), D. Levine (3), S. P. Riepe (3), R. A. van Hogezand (3), A. Ferguson (2), and B. D. Greenwald (1).