Background: Interleukin 10 (IL-10) is a cytokine which is intimately involved in the regulation of immune and inflammatory responses. Several studies have documented its essential role in preventing prolonged and exaggerated immune responses to antigens and irritants. In contrast to other inflammatory skin diseases decreased amounts of IL-10 have been detected in psoriatic skin. The role of IL-10 in psoriatic arthritis has not been studied. Objective: The safety, tolerance, immunologic effects and clinical activity of multiple doses of subcutaneous recombinant human IL-10 will be evaluated in a randomized, double-blind, placebo-controlled, escalating dose trial in patients with active psoriatic arthritis. Patients will receive a 28 day course of daily subcutaneous IL-10 (1.0, 5.0,10.0 or 20.0 mg/kg) or placebo. Disease activity (both skin and joints and toxicity) will monitored throughout the study. Research studies to be done include 1) functional assays of peripheral blood mononuclear cells; 2) cytokine expression (blood, synovium, skin); 3) activation of transcription factors specific for IL-10; 4) studies of the expression and function of tissue metalloproteinases and their inhibitors; 5) studies of lipid and bone turnover; and 6) MRI studies of synovial volume and inflammatory activity. Results Enrollment in the study has been completed and, to date, 29 patients have completed the trial. Infusions have been well tolerated with no serious adverse events observed. Analysis of the study is in progress. Lay Summary Interleukin 10 is an anti-inflammatory protein produced by certain types of cells in the body in order to prevent prolonged and intense inflammatory reactions to irritants. In patients with psoriasis, limited amounts of IL-10 can be found in the involved skin. In this study we have administered different doses of IL-10 (or no drug- placebo) in 29 patents with psoriatic arthritis and monitored its safety and efficacy. Analysis of the results of this clinical study is in progress. In addition to studying its clinical effects, we also examined how IL-10 exerts its effects in humans.
