Multiple doses of intravenous interleukin 10 in steroid-refractory Crohn's disease. Crohn's Disease Study Group.
OBJECTIVE
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 micrograms/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.
van Deventer
S J
SJ
Academic Medical Center, Amsterdam, The Netherlands.
Elson
C O
CO
Fedorak
R N
RN
D000328:Adult; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D016753:Interleukin-10 / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
D011994:Recombinant Proteins; D016753:Interleukin-10