IL-10 improves skin disease and modulates endothelial activation and leukocyte effector function in patients with psoriatic arthritis.
Psoriatic arthritis (PsA) provides an ideal disease model in which to investigate the bioactivities of potentially therapeutic cytokines at multiple sites of tissue inflammation. We investigated the effects of IL-10, an antiinflammatory cytokine, given s.c. for 28 days in a double-blind, placebo-controlled study in PsA patients. Synovial/skin biopsies, peripheral blood leukocytes, articular magnetic resonance images, and clinical disease activity scores were obtained sequentially. Modest, but significant clinical improvement in skin, but not articular disease activity scores with only minor adverse effects was observed. Type 1, but not type 2 T cell cytokine production in vitro was suppressed in human rIL-10 compared with placebo recipients. Similarly, monokine production in vitro was reduced, whereas serum soluble TNFRII levels were elevated, indicating suppression of monocyte function. Decreased T cell and macrophage infiltration in synovial tissues was accompanied by reduced P-selectin expression. Moreover, suppressed synovial enhancement on magnetic resonance imaging and reduced alpha(v)beta(3) integrin expression on von Willebrand factor(+) vessels were observed. Together these data demonstrate that a short course of IL-10 modulates immune responses in vivo via diverse effects on endothelial activation, and leukocyte recruitment and effector function. Such biological changes may result in clinically meaningful improvement in disease activity.
McInnes
I B
IB
Arthritis and Rheumatism Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Illei
G G
GG
Danning
C L
CL
Yarboro
C H
CH
Crane
M
M
Kuroiwa
T
T
Schlimgen
R
R
Lee
E
E
Foster
B
B
Flemming
D
D
Prussin
C
C
Fleisher
T A
TA
Boumpas
D T
DT
D000328:Adult; D015535:Arthritis, Psoriatic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D015331:Cohort Studies; D016207:Cytokines / Q000096:biosynthesis; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000276:immunology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology; D008279:Magnetic Resonance Imaging; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009389:Neovascularization, Pathologic; D012867:Skin / Q000276:immunology / Q000473:pathology; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D016207:Cytokines; D016753:Interleukin-10; D020782:Matrix Metalloproteinases