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Disease-dependent local IL-10 production ameliorates collagen induced arthritis in mice

Journal article
Authors Louise Henningsson
Tove Eneljung
Pernilla Jirholt
Sara Tengvall
Ulf Lidberg
Wim B van den Berg
Fons A van de Loo
Inger Gjertsson
Published in PLoS ONE
Volume 7
Issue 11
Pages e49731
ISSN 1932-6203
Publication year 2012
Published at Wallenberg Laboratory
Institute of Medicine, Department of Rheumatology and Inflammation Research
Pages e49731
Language en
Links dx.doi.org/10.1371/journal.pone.004...
https://gup.ub.gu.se/file/92128
Keywords tolerans, antiinflammatorisk, cytokin, inflammationsberoende, artrit, ledinflammation, reumatologi, ledgångsreumatism, antigen, musmodell, immunologi
Subject categories Basic Medicine

Abstract

Rheumatoid arthritis (RA) is a chronic destructive autoimmune disease characterised by periods of flare and remission. Today’s treatment is based on continuous immunosuppression irrespective of the patient’s inflammatory status. When the disease is in remission the therapy is withdrawn but withdrawal attempts often results in inflammatory flares, and re-start of the therapy is commenced when the inflammation again is prominent which leads both to suffering and increased risk of tissue destruction. An attractive alternative treatment would provide a disease-regulated therapy that offers increased anti-inflammatory effect during flares and is inactive during periods of remission. To explore this concept we expressed the immunoregulatory cytokine interleukin (IL)-10 gene under the control of an inflammation dependent promoter in a mouse model of RA - collagen type II (CII) induced arthritis (CIA). Haematopoetic stem cells (HSCs) were transduced with lentiviral particles encoding the IL-10 gene (LNT-IL-10), or a green fluorescence protein (GFP) as control gene (LNT-GFP), driven by the inflammation-dependent IL-1/IL-6 promoter. Twelve weeks after transplantation of transduced HSCs into DBA/1 mice, CIA was induced. We found that LNT-IL-10 mice developed a reduced severity of arthritis compared to controls. The LNT-IL-10 mice exhibited both increased mRNA expression levels of IL-10 as well as increased amount of IL-10 produced by B cells and non-B APCs locally in the lymph nodes compared to controls. These findings were accompanied by increased mRNA expression of the IL-10 induced suppressor of cytokine signalling 1 (SOCS1) in lymph nodes and a decrease in the serum protein levels of IL-6. We also found a decrease in both frequency and number of B cells and serum levels of anti-CII antibodies. Thus, inflammation-dependent IL-10 therapy suppresses experimental autoimmune arthritis and is a promising candidate in the development of novel treatments for RA.

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