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. DESIGN AND INTERVENTION: Patients received rhIL-10 (20 micro g/kg) or placebo subcutaneously 3 times weekly for 12 weeks in a randomized, double-blind manner. SETTING AND PATIENTS: 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. MAIN OUTCOME MEASURE: 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.
RCT Entities:
BACKGROUND: In several open-label studies, recombinant humaninterleukin 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. DESIGN AND INTERVENTION: Patients received rhIL-10 (20 micro g/kg) or placebo subcutaneously 3 times weekly for 12 weeks in a randomized, double-blind manner. SETTING AND PATIENTS: 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. MAIN OUTCOME MEASURE: 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.
Authors: Andrew M Donson; John Apps; Andrea M Griesinger; Vladimir Amani; Davis A Witt; Richard C E Anderson; Toba N Niazi; Gerald Grant; Mark Souweidane; James M Johnston; Eric M Jackson; Bette K Kleinschmidt-DeMasters; Michael H Handler; Aik-Choon Tan; Lia Gore; Alex Virasami; Jose Mario Gonzalez-Meljem; Thomas S Jacques; Juan Pedro Martinez-Barbera; Nicholas K Foreman; Todd C Hankinson Journal: J Neuropathol Exp Neurol Date: 2017-09-01 Impact factor: 3.685