Intra-articular IL-10 gene transfer regulates the expression of collagen-induced arthritis (CIA) in the knee and ipsilateral paw.
We studied the effects of local IL-10 application, introduced by a recombinant human type 5 adenovirus vector, in the mouse knee joint during the early phase of CIA. One intra-articular injection with the IL-10-expressing virus (Ad5E1mIL-10) caused substantial over-expression of IL-10 in the mouse knee joint, using virus dosages which did not induce distracting inflammation. High expression of IL-10 was noted for a few days, being maximal at day 1. One intra-articular injection of Ad5E1mIL-10 in the knee joints of collagen type II (CII)-immunized mice, before onset of CIA was noted, reduced the incidence of collagen arthritis in that knee. Of high interest, the protective effect of local IL-10 expression by Ad5E1mIL-10 was not restricted to the knee joint alone. The arthritis incidence in the ipsilateral paw was highly suppressed. In contrast, local IL-10 over-expression was not effective when treatment was started after onset of CIA. Further analysis in the acute streptococcal cell wall-induced arthritis model revealed that local IL-10 over-expression markedly suppressed the production of tumour necrosis factor-alpha (TNF-alpha) and IL-1alpha, but had no significant effect on IL-1beta and IL-12 production in the inflamed synovium. These data indicate that local over-expression of IL-10 in the knee joint of mice regulates the expression of collagen arthritis, probably through down-regulation of TNF-alpha.
Lubberts
E
E
Rheumatology Research Laboratory, Department of Rheumatology, University Hospital Nijmegen, Nijmegen, The Netherlands. E.Lubberts@reuma.azn.nl
Joosten
L A
LA
Van Den Bersselaar
L
L
Helsen
M M
MM
Bakker
A C
AC
Xing
Z
Z
Richards
C D
CD
Van Den Berg
W B
WB
D000260:Adenoviruses, Human / Q000276:immunology; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D002358:Cartilage, Articular; D003094:Collagen / Q000009:adverse effects; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000096:biosynthesis; D007719:Knee Joint / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D013583:Synovial Membrane / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D003094:Collagen