Clinical and immunologic assessment of patients with psoriasis in a randomized, double-blind, placebo-controlled trial using recombinant human interleukin 10.
BACKGROUND
In several open-label studies, recombinant human interleukin 10 (rhIL-10), a type 2 anti-inflammatory cytokine, has been reported to improve psoriasis, a disease characterized by type 1 cytokine inflammation.


OBJECTIVE
To evaluate the safety, efficacy, and immunologic parameters in individuals with psoriasis treated with rhIL-10.


METHODS
Patients received rhIL-10 (20 micro g/kg) or placebo subcutaneously 3 times weekly for 12 weeks in a randomized, double-blind manner.


METHODS
National Institutes of Health Clinical Center in Bethesda. Twenty-eight patients with moderate-to-severe psoriasis as defined by a Psoriasis Area Severity Index (PASI) score of 10 or higher.


METHODS
The primary clinical end point was the mean percentage change in the PASI score comparing baseline and week 12 scores. Intracellular cytokine production by peripheral blood mononuclear cells (PBMCs) was measured by flow cytometry.


RESULTS
There was no significant difference in the mean percentage change in the PASI score from baseline to week 12 between the rhIL-10-treated group and control patients (17% vs 13% improvement, respectively; P =.69), although a modest trend toward improvement in patients receiving rhIL-10 was documented at both the 6- and 8-week points. Interestingly, proinflammatory and type 1 cytokine production by PBMCs progressively declined in the rhIL-10-treated patients during the entire 12-week study period.


CONCLUSIONS
Treatment with rhIL-10 resulted in only temporary clinical improvement in psoriasis, despite sustained systemic decreases in proinflammatory and type 1 cytokine production. These data suggest that immunotherapy that decreases the ratio of systemic type 1 and type 2 cytokine production does not necessarily lead to improvement of type 1 cytokine-mediated disease.
Kimball
Alexa B
AB
Dermatology Branch, National Cancer Institute, Bethesda, MD 20892-1908, USA.
Kawamura
Tatsuyoshi
T
Tejura
Krupali
K
Boss
Carol
C
Hancox
Ana R
AR
Vogel
Jonathan C
JC
Steinberg
Seth M
SM
Turner
Maria L
ML
Blauvelt
Andrew
A
D000328:Adult; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007279:Injections, Subcutaneous; D016753:Interleukin-10 / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011336:Probability; D011565:Psoriasis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology*; D011995:Recombination, Genetic; D012016:Reference Values; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D016207:Cytokines; D016753:Interleukin-10